Despite the availability of different treatments for advanced NSCLC, all of them have a palliative intention and a cure for the disease is unlikely. Thus, advanced lung cancer remains as an unmet medical need. Chemoth...Despite the availability of different treatments for advanced NSCLC, all of them have a palliative intention and a cure for the disease is unlikely. Thus, advanced lung cancer remains as an unmet medical need. Chemotherapy has been used as the therapy of choice for advanced NSCLC patients, but it is mainly limited by the patient’s performance status. More recently, targeted therapies have introduced more specific treatment options that show efficacy in specific niche of patients, but precisely due to their target specificity, they usually provoke early resistance. In addition to these limitations, most of the best drugs currently used for treatment of advanced NSCLC show small increases in patient survival with severe associated toxicity. Novel drugs with low toxicity that could be given chronically to control the advanced disease can make a difference. They could allow the management of advanced cancer as a chronic disease that, even when not cured, it can be controlled for long periods of time offering patients a good quality of life. Active-specific immunotherapy is an area of oncology that is rapidly expanding with encouraging results. Cancer vaccines against many potential targets have shown to increase patient survival in clinical trials at all stages NSCLC, when included as first-line, maintenance, or second-line therapy. Safety of cancer vaccines supposes a new hope for cancer therapy, and this unique characteristic makes it possible to be used in sub-sets of patients that cannot receive other approved treatments because of their high toxicity. In this paper, authors propose how active immunotherapy could be included in the current algorithm for treatment of advanced NSCLC patients.展开更多
Objective To investigate the effect of active immunotherapy on unexplained recurrent spontaneous abortion (URSA ) during the process of gestation and delivery period. Methods We collected the data of the women with ...Objective To investigate the effect of active immunotherapy on unexplained recurrent spontaneous abortion (URSA ) during the process of gestation and delivery period. Methods We collected the data of the women with URSA and their offsprings. The women were treated by immunization with paternal lymphocytes and then had a successful pregnancy. The fore mentioned group of women were compared with those who had a normal pregnancy and then delivered in the same period. Results The incidences of premature rupture of membranes, adherent placenta, and residual cauls in the group of URSA patients were statistically higher than those in the normal group. Correspondingly, gestational age at delivery and birth weight of the newborns of the group of URSA patients were lower, but there were no significant differences between the two groups. Conclusion These results indicate that paternal lymphocyte immunotherapy is effective on the maintenance of pregnancy in women with URSA, and has no deleterious effects on the fetus or newborns. However, in case of the higher incidence of premature rupture of membranes, adherent placenta, and residual cauls, more attention should be paid to the treated patients to avoid intrauterine growth retardation and postpartum hemorrhage.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers wor...Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.展开更多
Lynch syndrome is the fourth most common cancer in the United States, with an early age of onset and poor prognosis. Here, we present a unique case of a patient with progressive colon cancer due to a late diagnosis of...Lynch syndrome is the fourth most common cancer in the United States, with an early age of onset and poor prognosis. Here, we present a unique case of a patient with progressive colon cancer due to a late diagnosis of Lynch syndrome showing excellent response to immunotherapy. A 59-year-old male with a history of rectal cancer 30 years ago came to the hospital due to a fever and further found a large necrotic colon mass. Biopsy was positive for colorectal cancer;however, due to the size of the tumor, the patient was deemed not a surgical candidate and offered hospice with palliative chemotherapy. Based on further workup, the patient was diagnosed with Lynch syndrome, with colon cancer determined to be responsive to Immunotherapy. He was started on JEMPERLI (Dosterlimab-gxly), and after three cycles of therapy, imaging and PET scan were repeated, showing decreased activity and extent of the tumor—a tremendous success.展开更多
Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of im...Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.展开更多
Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream...Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream methods that target T and natural killer(NK)cells,B cell-associated anti-tumor immunotherapy is promising。展开更多
This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer(GC).Our study reviews recent advances in immunotherapy in the ...This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer(GC).Our study reviews recent advances in immunotherapy in the field of GC and highlights its new prospects as a treatment for GC.Our research reveals China’s leadership in this field,as well as new therapeutic strategies such as immune checkpoint inhibitors,cellular immunotherapy,and vaccines.The combined findings highlight the potential of immunotherapy to improve survival and quality of life in patients with stomach cancer.We believe that this study will provide important guidance for the future direction of the GC treatment field.展开更多
Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was ...Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.展开更多
Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppre...Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.展开更多
Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death p...Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.展开更多
In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent...In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.展开更多
The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel prote...The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.展开更多
BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further stu...BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.展开更多
BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due t...BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual differences.Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival rates.Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately considered.AIM To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy.METHODS Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways.Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells.The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related features.Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model.Finally,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene signature.RESULTS The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell communication.The effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltration analysis,survival analysis,and expression analysis.CONCLUSION The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment,providing insights for personalized treatment strategies.展开更多
Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a ca...Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.展开更多
With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors...With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.展开更多
Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high c...Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.展开更多
BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more effi...BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.展开更多
Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data...Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.展开更多
文摘Despite the availability of different treatments for advanced NSCLC, all of them have a palliative intention and a cure for the disease is unlikely. Thus, advanced lung cancer remains as an unmet medical need. Chemotherapy has been used as the therapy of choice for advanced NSCLC patients, but it is mainly limited by the patient’s performance status. More recently, targeted therapies have introduced more specific treatment options that show efficacy in specific niche of patients, but precisely due to their target specificity, they usually provoke early resistance. In addition to these limitations, most of the best drugs currently used for treatment of advanced NSCLC show small increases in patient survival with severe associated toxicity. Novel drugs with low toxicity that could be given chronically to control the advanced disease can make a difference. They could allow the management of advanced cancer as a chronic disease that, even when not cured, it can be controlled for long periods of time offering patients a good quality of life. Active-specific immunotherapy is an area of oncology that is rapidly expanding with encouraging results. Cancer vaccines against many potential targets have shown to increase patient survival in clinical trials at all stages NSCLC, when included as first-line, maintenance, or second-line therapy. Safety of cancer vaccines supposes a new hope for cancer therapy, and this unique characteristic makes it possible to be used in sub-sets of patients that cannot receive other approved treatments because of their high toxicity. In this paper, authors propose how active immunotherapy could be included in the current algorithm for treatment of advanced NSCLC patients.
文摘Objective To investigate the effect of active immunotherapy on unexplained recurrent spontaneous abortion (URSA ) during the process of gestation and delivery period. Methods We collected the data of the women with URSA and their offsprings. The women were treated by immunization with paternal lymphocytes and then had a successful pregnancy. The fore mentioned group of women were compared with those who had a normal pregnancy and then delivered in the same period. Results The incidences of premature rupture of membranes, adherent placenta, and residual cauls in the group of URSA patients were statistically higher than those in the normal group. Correspondingly, gestational age at delivery and birth weight of the newborns of the group of URSA patients were lower, but there were no significant differences between the two groups. Conclusion These results indicate that paternal lymphocyte immunotherapy is effective on the maintenance of pregnancy in women with URSA, and has no deleterious effects on the fetus or newborns. However, in case of the higher incidence of premature rupture of membranes, adherent placenta, and residual cauls, more attention should be paid to the treated patients to avoid intrauterine growth retardation and postpartum hemorrhage.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金Supported by The Scientific Initiation Scholarship Programme(PIBIC)of National Council for Scientific and Technological Development,CNPq,Brazil(Luz MS and Pinheiro SLR),No.6511185733054315 and No.3748771590681149The coauthor Lemos,FFB is supported by the Scientific Initiation Scholarship Programme(PIBIC)of Bahia State Research Support Foundation,FAPESB,Brazil,No.19.573.301.5418and the CNPq Research Productivity Fellow(de Melo FF),No.4357511882624145.
文摘Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency.It is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive cells.Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy for cancer patients and,consequently,a reduction in the lethality of this aggressive cancer.
文摘Lynch syndrome is the fourth most common cancer in the United States, with an early age of onset and poor prognosis. Here, we present a unique case of a patient with progressive colon cancer due to a late diagnosis of Lynch syndrome showing excellent response to immunotherapy. A 59-year-old male with a history of rectal cancer 30 years ago came to the hospital due to a fever and further found a large necrotic colon mass. Biopsy was positive for colorectal cancer;however, due to the size of the tumor, the patient was deemed not a surgical candidate and offered hospice with palliative chemotherapy. Based on further workup, the patient was diagnosed with Lynch syndrome, with colon cancer determined to be responsive to Immunotherapy. He was started on JEMPERLI (Dosterlimab-gxly), and after three cycles of therapy, imaging and PET scan were repeated, showing decreased activity and extent of the tumor—a tremendous success.
基金supported by grants from the National Natural Science Foundation of China (Grant No. U20A20369)GuangDong Basic and Applied Basic Research Foundation (Grant No. 2022B1515120085)。
文摘Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.
文摘Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream methods that target T and natural killer(NK)cells,B cell-associated anti-tumor immunotherapy is promising。
基金the Discipline Promotion Program of Shanghai Fourth People’s Hospital,No.SY-XKZT-2020-1021.
文摘This letter is intended to arouse your interest in a recent review of comprehensive scientometrics and clinical trials on immunotherapy for gastric cancer(GC).Our study reviews recent advances in immunotherapy in the field of GC and highlights its new prospects as a treatment for GC.Our research reveals China’s leadership in this field,as well as new therapeutic strategies such as immune checkpoint inhibitors,cellular immunotherapy,and vaccines.The combined findings highlight the potential of immunotherapy to improve survival and quality of life in patients with stomach cancer.We believe that this study will provide important guidance for the future direction of the GC treatment field.
文摘Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.
文摘Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.
基金Supported by Natural Science Foundation of Fujian Province,No.2021J011259.
文摘Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.
文摘In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of Gastroenterology.We focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 years.Before that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the neoplasm.We then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant neoplasm.We describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)cases.Special attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with chemotherapy.There is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in progress.Finally,an attempt is made to draw some conclusions and to point out possible future directions.
基金the National Key Research and Development Program of China(Grant Nos.2022YFC3401500 and 2020YFA0803201 to P.W.,and 2021YFA1302200 to L.F.)the National Natural Science Foundation of China(Grant Nos.31830053,31920103007,and 82341028 to P.W.+1 种基金82122056,82073153,and 31871398 to L.F.and 31900568 to P.W.)the Natural Science Foundation of Shanghai(Grant No.22ZR1450700 to Z.J.W.)。
文摘The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.
基金Our study has been approved by Medical Research Ethics Approval Committee(2023010122HN11C).
文摘BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.
基金Supported by Scientific and Technological Project of Henan Province,No.212102210140.
文摘BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual differences.Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival rates.Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately considered.AIM To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy.METHODS Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways.Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells.The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related features.Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model.Finally,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene signature.RESULTS The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell communication.The effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltration analysis,survival analysis,and expression analysis.CONCLUSION The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment,providing insights for personalized treatment strategies.
基金was supported by National Natural Science Foundation of China(81972893,82172719)Natural Science Foundation of Henan(212300410071)Training program for young key teachers in Henan Province(2020GGJS019).
文摘Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.
文摘With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.
基金This work is supported by National Key Research and Development Program of China(No.2022YFC3501905)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)+2 种基金National Natural Science Foundation of China(NSFC,No.82104076)Science and Technology Commission of Shanghai Municipal(STCSM,No.22S21902400,China)Medicine-Engineering joint foundation of Shanghai Jiao Tong University(No.YG2022QN025 and YG2022QN050,China).
文摘Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.
基金This study was reviewed and approved by the Ethics Committee of Zhongshan People’s Hospital(Approval No.2022-029).
文摘BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.
基金supported by the National Innovation and Enterpreneurship Training Program for College Students(202210367002)the Key Laboratory Open Project of An-hui Province(AHCM2022Z004).
文摘Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.