Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

Peptide drugs: a new direction in cancer immunotherapy

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.

Gastric cancer immunotherapy:A scientometric and clinical trial review

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.

Emerging mechanisms and implications of c GAS-STING signaling in cancer immunotherapy strategies

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.

Approaches and challenges in cancer immunotherapy pathways

Cancer immunotherapy is an effective with critical approaches in the treatment of oncological patients.Whilst numerous research and clinical trials are underway to develop endogenous immunotherapy approaches,it is necessary to focus on fundamental issues and identify barriers to basic clinical progress.Addressing these challenges and the new pathways will require researchers and clinicians to join forces to accelerate the understanding of the complex interactions between cancer and the immune system and focus resources on developing better treatments for patients.

Current applications and future prospects of nanotechnology in cancer immunotherapy

Cancer immunotherapy is an artificial stimulation of the immune system to recognize cancer cells and activate specific immune cells to target and attack cancer cells.In clinical trials, immunotherapy has recently shown impressive results in the treatment of multiple cancers.Thus, cancer immunotherapy has gained a lot of attention for its unique advantages and promising future.With extensive research on cancer immunotherapy, its safety and effectiveness has gradually been revealed.However, it is still a huge challenge to expand and drive this therapy while maintaining low toxicity, high specificity, and long-lasting efficacy.As a unique technology, nanotechnology has been applied in many fields, the advantages of which will promote the development of cancer immunotherapies.Researchers have tried to apply nanomaterials to cancer immunotherapy due to their advantageous properties,such as large specific surface areas, effective drug delivery, and controlled surface chemistry, to improve treatment efficacy.Here,we briefly introduce the current applications of nanomaterials in cancer immunotherapy, including adoptive cell therapy(ACT),therapeutic cancer vaccines, and monoclonal antibodies, and throw light on future directions of nanotechnology-based cancer immunotherapy.

PD-1/PD-L1 pathway blockade works as an effective and practical therapy for cancer immunotherapy

Cancer immunotherapy has greatly advanced in recent years,and PD-1/PD-L1 blocking therapy has become a major pillar of immunotherapy.Successful clinical trials of PD-1/PD-L1 blocking therapies in cancer treatments have benefited many patients,which promoted the Food and Drug Administration(FDA)approval of PD-1/PD-L1 blocking drugs.In this review,we provide a detailed introduction of five PD-1/PD-L1 blocking drugs,with indications and studies,as a valuable reference for doctors and medical investigators.Moreover,the characteristics of PD-1/PD-L1 blocking therapies,including their universality and sustainability,are discussed in this review.Furthermore,we also discuss and predict the possibility of PD-L1 as an indication marker of PD-1/PD-L1 blocking therapy for pan-cancer treatment,and the current status of combination therapies.

Dendritic cell-based cancer immunotherapy for colorectal cancer

Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.

Role of nanoparticle-mediated immunogenic cell death in cancer immunotherapy

An essential concept of cancer immunotherapy is that immunogenic cell death(ICD),characterized by the release of tumor-associated antigens(TAAs)and tumor-specific antigens(TSAs)like neoantigens,danger-associated molecular patterns(DAMPs),and pro-inflammatory cytokines,facilitates the presentation of TAAs and TSAs to adaptive immune cells,eliciting an emerging or reinstating a pre-existing anti-cancer immune response.

Immunosuppressive checkpoint Siglec-15:a vital new piece of the cancer immunotherapy jigsaw puzzle

On March 5th, a novel immunosuppressive molecule,Siglec-15, was reported in Nature Medicine by Professor Lieping Chen1. Siglec-15 was reported in a wide variety of tumors. The molecule is not a simple replica of PD-1/PD-L1.Rather, the expressions of Siglec-15 and PD-L1 are mutually exclusive1, suggesting that Siglec-15 antibodies may be effective on tumors that are not responsive to anti-PD-1/PDL1 therapy. Siglec-15 potentially serves as a complementary therapeutic target and offers alternative treatments for many anti-PD-l/PD-Ll therapy unresponsive patients. This discovery generated a huge response.

Assays for predicting and monitoring responses to lung cancer immunotherapy

Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer （NSCLC）. Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry （IHC） with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-I/PD-L1 pathway.

Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023)

BACKGROUND Gastric cancer(GC)is the sixth most common cancer and third leading cause of cancer-related deaths worldwide.Current treatments mainly rely on surgery-and chemotherapy-based systemic;however,the prognosis remains poor for advanced disease.Recent studies have suggested that immunotherapy has significant potential in cancer therapy;thus,GC immunotherapy may improve quality of life and survival for patients with this disease.AIM To provide a comprehensive overview of the knowledge structure and research hotspots of GC immunotherapy.METHODS We conducted a bibliometric analysis of publications on immunotherapy related to GC in the Web of Science Core Collection database.We analyzed 2013 publications from 1999 to February 1,2023,using the VOSviewer and CiteSpace software.We assessed publication and citation distributions using the WoS platform and explored research countries,institutions,journals,authors,references,and keywords(co-occurrence,timeline view,and burst analysis).In addition,we examined 228 trials on immunotherapy,137 on adoptive cell therapy,274 on immune checkpoint inhibitors(ICIs),and 23 on vaccines from ClinicalTrials.gov and the International Clinical Trials Registry Platform.The Impact Index Per Article for the top ten high-cited papers collected from Reference Citation Analysis(RCA)are presented.RESULTS Our bibliometric analysis revealed that the study of immunotherapy in GC has developed rapidly in recent years.China accounted for almost half the publications,followed by the United States.The number of publications in recent years has been growing continuously,and most institutions and authors with the most publications are from China.The main keywords or clusters identified were“tumor microenvironment”,“adoptive immunotherapy”,“dendritic therapy”,and“microsatellite instability”.CONCLUSION Our analysis of 2013 publications indicated that immunotherapy for GC has led to several new developments in recent years.Considerable progress has been made in vaccinations,immune checkpoint therapy,and adoptive cellular therapy.In particular,ICIs and chimeric antigen receptor T-cells are novel options for the treatment of GC.We suggest that the combination of ICIs,chemotherapy,targeted therapy,and other immunotherapies should be the primary research direction in the future.

Myeloid checkpoints for cancer immunotherapy

Myeloid checkpoints are receptors on the myeloid cell surface which can mediate inhibitory signals to modulate anti-tumor immune activities.They can either inhibit cellular phagocytosis or suppress T cells and are thus involved in the pathogenesis of various diseases.In the tumor microenvironment,besides killing tumor cells by phagocytosis or activating anti-tumor immunity by tumor antigen presentation,myeloid cells could execute protumor efficacies through myeloid checkpoints by interacting with counter-receptors on other immune cells or cancer cells.In summary,myeloid checkpoints may be promising therapeutic targets for cancer immunotherapy.

Red Blood Cell-Mimic Nanocatalyst Triggering Radical Storm to Augment Cancer Immunotherapy

Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue.Herein,artificial RBCs(designated FTP@RBCM)with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal-organic frameworks(FTPs,as the core),including photodynamic/chemodynamic-like,catalase-like and glutathione peroxidase-like activities.Meanwhile,owing to the advantages of long circulation abilities of RBCs provided by their cell membranes(RBCMs),FTP with a surface coated with RBCMs(FTP@RBCM)could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency.Intriguingly,this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death,which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3(Tim-3)checkpoint blockade,leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors.Therefore,such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.

Smart drug delivery systems to overcome drug resistance in cancer immunotherapy

Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.

Artificial Nanoscale Erythrocytes from Clinically Relevant Compounds for Enhancing Cancer Immunotherapy

Because of enhanced e cacy and lower side e ects,cancer immunotherapies have recently been extensively investigated in clinical trials to overcome the limitations of conventional cancer monotherapies.Although engineering attempts have been made to build nanosystems even including stimulus nanomaterials for the e cient delivery of antigens,adjuvants,or anticancer drugs to improve immunogenic cancer cell death,this requires huge R&D e orts and investment for clinically relevant findings to be approved for translation of the nanosystems.To this end,in this study,an air–liquid two-phase electrospray was developed for stable bubble pressing under a balance between mechanical and electrical parameters of the spray to continuously produce biomimetic nanosystems consisting of only clinically relevant compounds[paclitaxel-loaded fake blood cell Eudragit particle(Eu-FBCP/PTX)]to provide a conceptual leap for the timely development of translatable chemo-immunotherapeutic nanosystems.This was pursued as the e cacy of systems for delivering anticancer agents that has been mainly influenced by nanosystem shape because of its relevance to transporting behavior to organs,blood circulation,and cell–membrane interactions.The resulting Eu-FBCP/PTX nanosystems exhibiting phagocytic and micropinocytic uptake behaviors can confer better e cacy in chemo-immunotherapeutics in the absence and presence of anti-PD-L1 antibodies than similar sized PTX-loaded spherical Eu particles(Eu-s/PTX).

The roles of toll-like receptors in carcinogenesis and cancer immunotherapy

Toll-like receptors （TLRs） are probably the most important class of pattern-recognition receptors. Members of the TLR family play key roles in the both innate and adaptive immune responses. Recognition of pathogen-associated molecular patterns （PAMPs） by TLRs, either alone or in heterodimedzation with other TLR or non-TLR receptors, induces the production of signals that are responsible for the activation of genes important for an effective host defense, especially those of proinflammatory cytokines. Thus, TLRs are involved in the development of many pathological conditions including infectious diseases, tissue damage, and cancer especially. In this review, the contribution of TLRs to tumorgenesis is evaluated. We hope to provide new insight into the progression of cancer and more importantly into the potential for TLRs as targets of therapeutics.

Use of traditional Chinese medicine in the treatment of immune-related adverse events of cancer immunotherapy

Immune checkpoint inhibitors(ICPI)have shown considerable promise in the treatment of tumors.However,immune-related adverse events(irAEs)caused by ICPI have been reported in nearly every organ system.Whilst this represents a new challenge in the field of cancer treatment,traditional Chinese medicine(TCM)provides benefits in the treatment of irAEs.This article reviews the studies of the treatment of immune-related gastrointestinal diseases and dermatosis with TCM and introduces the collaborative efforts between China and France in the implementation of TCM for the treatment of irAEs.

Nanomaterials for modulating innate immune cells in cancer immunotherapy

Cancer immunotherapy has been intensively investigated in both preclinical and clinical studies.Whereas chemotherapies use cytotoxic drugs to kill tumor cells,cancer immunotherapy is based on the ability of the immune system to fight cancer.Tumors are intimately associated with the immune system:they can suppress the immune response and/or control immune cells to support tumor growth.Immunotherapy has yielded promising results in clinical practice,but some patients show limited responses.This may reflect the complexities of the relationship between a tumor and the immune system.In an effort to improve the current immunotherapies,researchers have exploited nanomaterials in creating new strategies to cure tumors via modulation of the immune system in tumor tissues.Although extensive studies have examined the use of immune checkpoint-based immunotherapy,rather less work has focused on manipulating the innate immune cells.This review examines the recent approaches and challenges in the use of nanomaterials to modulate innate immune cells.

Using triple radio-immunotherapy to overcome cancer immunotherapy resistance

Cancer is a widespread public health issue and has become a leading cause of death in most countries.In recent decades,immunotherapy,particularly the use of immune checkpoint inhibitors(ICIs),has altered the clinical practice of cancer treatment and evolved into a first-line clinical strategy.