Aggressive natural killer cell leukemia with skin manifestation associated with hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Aggressive natural killer cell leukemia(ANKL)is a rare natural killer cell neoplasm characterized by systemic infiltration of Epstein–Barr virus and rapidly progressive clinical course.ANKL can be accompanied with hemophagocytic lymphohistiocytosis(HLH).Here,we report a case of ANKL with rare skin lesions as an earlier manifestation,accompanied with HLH,and review the literature in terms of etiology,clinical manifestation,diagnosis and treatment.CASE SUMMARY A 30-year-old woman from Northwest China presented with the clinical characteristics of jaundice,fever,erythema,splenomegaly,progressive hemocytopenia,liver failure,quantities of abnormal cells in bone marrow,and associated HLH.The immunophenotypes of abnormal cells were positive for CD2,cCD3,CD7,CD56,CD38 and negative for sCD3,CD8 and CD117.The diagnosis of ANKL complicated with HLH was confirmed.Following the initial diagnosis and supplementary treatment,the patient received chemotherapy with VDLP regimen(vincristine,daunorubicin,L-asparaginase and prednisone).However,the patient had severe adverse reactions and complication such as severe hematochezia,neutropenia,and multiple organ dysfunction syndrome,and died a few days later.CONCLUSION This is the first reported case of ANKL with rare skin lesions as an earlier manifestation and associated with HLH.

REGULATORY EFFECTS OF HUMAN RECOMBINANT IL-6 ON NATURAL KILLER CELL ACTIVITY OF HUMAN FETAL SPLEENS

In the present study it was proved first that human recombinant interleukin-6(HrIL-6) significantly augmented natural killer(NK) cell activity derived from human fetal spleens against K562 target cells in a 4 hours 51Cr release assay. The enhancement of NK activity with 24 hours preincubation in HrlL-6 was dose-dependent, and significantly higher than that of fresh NK cells and controls cultured with RPMI-1640 medium alone (P<0.001). We also found that IL-6 was able to augment NK activity from different fetal spleens at 20 to 40 weeks of gestation (up to 2.24 to 2.78 times), and no difference of NK activity of fetal splenocytes treated by HrIL-6 was observed between different fetal age (32.3% to 45.4%, P>0.05). Furthermore, IL-6-augmented NK activity of fetal splenocytes was very similar to adult levels (P>0.05). These finding strongly indicated that IL-6 plays an important role in the development of NK cell function during the gestational period, suggesting that IL-6 may be of importance in the regulation of host defense mechanisms against malignancies and viral diseases.

Effects of acupuncture treatment on natural killer cell activity,pulse rate,and pain reduction for older adults:an uncontrolled,observational study

OBJECTIVE： The aim of this study was to examine the changes in natural killer （NK） cell activity, pulse rate, and pain intensity among older adults before and after acupuncture treatment. METHODS： Fifty-six individuals （16 males and 40 females）, aged 60 to 82 years （mean age 72.4 ＋ 5.0）, who were experiencing pain in the shoulder, low back, or knee, participated in the study. NK cell activity, leukocyte differentiation （granulocytes and lymphocytes）, pulse rate, and blood pressure values were obtained. Pain intensity was evaluated by using the visual analog scale （VAS）. The Wilcoxon test was used to analyze NK cell activity, leukocytes （granulocyte counts and granulocyte-to-lymphocyte ratio）, and the VAS score in accordance with the location of pain complaints before and after acupuncture treatment. RESULTS： NK cell activity decreased after acupuncture treatment for pain in the shoulder-pain and knee-pain groups. Further, the lymphocyte and granulocyte counts increased after acupuncture treatment for the shoulder-pain group. Pulse rate decreased for the shoulder-pain, low-back- pain, and knee-pain groups after acupuncture treatment. The VAS score decreased after acupuncture treatment for the shoulder-pain, low-back-pain, and knee-pain groups. CONCLUSION： This study showed that in older adults, acupuncture treatment decreases pulse rate, relieves pain in the shoulder, low back, and knee, and reduces NK-cell activity.

Inositol hexaphosphate-induced enhancement of natural killer cell activity correlates with suppression of colon carcinogenesis in rats

AIM： To investigate the anti-neoplastic effect of inositol hexaphosphate （InsP6 or phytic acid） on dimethylhydrazine （DMH）-induced colon tumor in rats and its effect on blood natural killer （NK） cell activity. METHODS： Healthy Wistar rats, 4 wk old, were divided into control group （fed with common food） and InsP6 group （fed with common food＋2% sodium inositol hexaphosphate in the drinking water）, 15 rats in each group. Both groups were injected with 1,2-dimethylhydrazine subcutaneously （20 mg/kg body weight） once a week for 20 wk. Rats were killed after 21 wk. The whole large intestine was isolated to determine the general condition of tumors and to test blood NK cell activity by lactate-dehydrogenase-release assay. RESULTS： Administration of InsP6 significantly increased blood NK cell activity in DMH-induced colorectal tumor in rats. InsP6 group had a smaller tumor size on average and a smaller number of tumors than the control group. Its mortality was also higher than that in control. However, the variables of body weight and tumor incidence were not significantly different between the two groups. CONCLUSION： InsP6 can increase blood NK cell activity in DMH-induced colon tumor in rats and inhibit tumor growth and metastasis in rats.

Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers

Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products.Methods:We constructed a trispecific killer engager(TriKE)consisting of anti-CD16,IL-15,and anti-CD19.This TriKE was designed to attract CD19^(+)tumor cells to CD16^(+)NK cells,whereas IL-15 sustained the proliferation,development,and survival of NK cells.Results:Treatment with 161519 TriKE in the presence of CD19^(+)targets upregulated expression of CD69,CD107 a,TRAIL,IFN-γ,and TNF-α in NK cells,and significantly improved the proliferation and cytotoxicity of NK cells.NK cells"armed"with 161519 TriKE showed stronger cytolysis against CD19+targets compared with that of"unarmed"NK cells.A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE,when compared with that in control mice or mice treated with 1619 BiKE.Combined use of IL-2 was a more effective treatment with 1619 BiKE,when compared with that using 161519 TriKE.Conclusions:The newly generated 161519 TriKE enhanced the proliferation,activation,cytokine secretion,and cytotoxicity of NK cells in the presence of CD19+tumor cells.The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts,and could be used to treat CD19-positive cancers.

Potential of Natural Killer Cell Enriched Conditioned Media for Skin Care and Anti-Aging

Natural killer (NK) cell is a type of immune cell and is known to be particularly responsible for innate immunity such as anti-cancer immunity, defense mechanisms against infections, and secretion of various cytokines and chemokines for increasing recruitment of other immune cells. In this study, we investigated the potentials of NK-enriched lymphocytes (NKEL) conditioned media (CM) on skin care for cosmeceutical compositions. Various cytokines of NKEL CM can improve wound healing through epithelial-mesenchymal transition (EMT) by increasing KLKs (kallikreins) and reduce metalloproteinase (MMP)-1 and MMP-2 to inhibit wrinkle formation. Our results suggest that NKEL CM which has various cytokines promotes up-regulation of cell migration and KLKs and down-regulation of MMP-1 and MMP-2 by stimulating HaCaT keratinocytes migration. Therefore, NKEL CM can be used as a cosmetic composition that can play a role in skin regeneration and anti-aging.

Clinical Detection of Peripheral Blood Natural Killer Cell Activity

Natural Killer (NK) cells are specific immune cells in human immune system. They have a quick effect and can exert a cytotoxic function without prior sensitization, and they show great application potential in cell-based immunotherapy, anti-infection in vivo. NK cell activity in peripheral blood can be used as one of the biomarkers of immune function response. It has a great positive guiding significance for the clinical prognosis of tumor patients, the prevention of cancer and anti-aging. The clinical detection strategies of NK cell activity in circulation mainly grouped into five types: methyl thiazolyl tetrazolium colorimetric, lactate dehydrogenase release, radionuclide labeling, flow cytometry and NK Vue cytokine release method. It has played an important role in different stages of clinical application development. This paper will make a comparative review of the above-mentioned detection strategies for the NK cell activity.

Stabilizing perovskite precursors with the reductive natural amino acid for printable mesoscopic perovskite solar cells

Solution processability significantly advances the development of highly-efficient perovskite solar cells.However,the precursor solution tends to undergo irreversible degradation reactions,impairing the device performance and reproducibility.Here,we utilize a reductive natural amino acid,Nacetylcysteine(NALC),to stabilize the precursor solution for printable carbon-based hole-conductorfree mesoscopic perovskite solar cells.We find that I_(2) can be generated in the aged solution containing methylammonium iodide(MI) in an inert atmosphere and speed up the MA-FA^(+)(formamidinium) reaction which produces large-size cations and hinders the formation of perovskite phase.NALC effectively stabilizes the precursor via its sulfhydryl group which reduces I_(2) back to I^(-)and provides H^(+).The NALC-stabilized precursor which is aged for 1440 h leads to devices with a power conversion efficiency equivalent to 98% of that for devices prepared with the fresh precursor.Furthermore,NALC improves the device power conversion efficiency from 16.16% to 18.41% along with enhanced stability under atmospheric conditions by modifying grain boundaries in perovskite films and reducing associated defects.

Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion:A case report

BACKGROUND Intestinal natural killer/T-cell lymphoma(NKTCL)is a rare and aggressive non-Hodgkin’s lymphoma,and its occurrence is closely related to Epstein-Barr virus infection.In addition,the clinical symptoms of NKTCL are not obvious,and the specific pathogenesis is still uncertain.While NKTCL may occur in any segment of the intestinal tract,its distinct location in the periampullary region,which leads clinicians to consider mimics of a pancreatic head mass,should also be addressed.Therefore,there remain huge challenges in the diagnosis and treatment of intestinal NKTCL.CASE SUMMARY In this case,we introduce a male who presented to the clinic with edema of both lower limbs,accompanied by diarrhea,and abdominal pain.Endoscopic ultrasound(EUS)showed well-defined homogeneous hypoechoic lesions with abundant blood flow signals and compression signs in the head of the pancreas.Under the guidance of EUS-fine needle biopsy(FNB)with 19 gauge or 22 gauge needles,combined with multicolor flow cytometry immunophenotyping(MFCI)helped us diagnose NKTCL.During treatments,the patient was prescribed the steroid(dexamethasone),methotrexate,ifosfamide,L-asparaginase,and etoposide chemotherapy regimen.Unfortunately,he died of leukopenia and severe septic shock in a local hospital.CONCLUSION Clinicians should enhance their understanding of NKTCL.Some key factors,including EUS characteristics,the right choice of FNB needle,and combination with MFCI,are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.

Immune evasion and therapeutic opportunities based on natural killer cells

Natural killer(NK)cells can elicit an immune response against malignantly transformed cells without recognizing antigens,and they also exhibit cytotoxic effects and immune surveillance functions in tumor immunotherapy.Although several studies have shown the promising antitumor effects of NK cells in immunotherapy,their function is often limited in the tumor microenvironment because tumor cells can easily escape NK cell-induced death.Thus,for efficient tumor immunotherapy,the mechanism by which tumor cells escape NK cell-induced cytotoxicity must be fully understood.Various novel molecules and checkpoint receptors that mediate the disruption of NK cells in the tumor microenvironment have been discovered.In this review,we analyze and detail the major activating and inhibitory receptors on the surface of NK cells to delineate the mechanism by which tumor cells suppress NKG2D ligand expression and increase tumor receptor and inhibitory receptor expression[NKG2A,programmed cell death1(PD-1),and T-cell immunoglobulin and immunoreceptor tyrosine inhibitory motif(TIGIT)]on the NK cell surface,and thus inhibit NK cell activity.We also reviewed the current status of treatments based on these surface molecules.By comparing the therapeutic effects related to the treatment status and bypass mechanisms,we attempt to identify optimal single or combined treatments to suggest new treatment strategies for tumor immunotherapy.

Designing a risk prognosis model based on natural killer cell-linked genes to accurately evaluate the prognosis of gastric cancer

Background:This study was aimed at identifying natural killer(NK)cell-related genes to design a risk prognosis model for the accurate evaluation of gastric cancer(GC)prognosis.Methods:We obtained NK cell-related genes from various databases,followed by Cox regression analysis and molecular typing to identify prognostic genes.Various immune algorithms and enrichment analyses were used to investigate the mutations,immune status,and pathway variations among different genotypes.The key prognostic genes were assessed using the least absolute shrinkage and selection operator(Lasso)regression analysis and univariate Cox regression analysis.Thereafter,the risk score(RS)prognosis model was constructed based on the selected important prognostic genes.A Receiver Operating Characteristics(ROC)curve was plotted for analyzing the robustness of the model.Subsequently,the decision and calibration curves were used for assessing the reliability and prediction accuracy of the proposed model.The‘pRRophetic’R software package was utilized for predicting the half-maximal inhibitory concentration(IC50)of immunotherapy and chemotherapy drugs.Results:We screened 21 prognostic genes and three molecular subtypes and found that the C1 subtype had the worst prognosis.Further,the pathways promoting tumor proliferation,such as epithelial-mesenchymal transition were significantly up-regulated.The results also showed that the macrophages in the M2 stage were significantly infiltrated in the C1 subtype,and there was significant overexpression in the C1 subtype,accompanied by a severe inflammatory reaction.The C1 was highly sensitive to drugs like 5-fluorouracil and paclitaxel.The ROC,calibration curve,and decision curve showed that the risk model was robust and strongly reliable.Conclusion:Overall,our proposed NK cell-related RS model can be used as a more accurate prediction index for GC patients,providing a valuable contribution to personalized medicine.

Establishment of a prognostic model related to tregs and natural killer cells infiltration in bladder cancer

BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.

Diffuse large B-cell lymphoma successfully treated with amplified natural killer therapy alone: A case report

BACKGROUND The prognosis of patients with advanced diffuse large B-cell lymphoma(DLBCL)is poor,with a 5-year survival rate of approximately 50%.The mainstay of treatment is multidrug combination chemotherapy,which has been associated with serious side effects.Amplified natural killer(ANK)cell therapy amplifies and activates natural killer(NK)cells to attack only malignant tumors.As ANK cells attack programmed death ligand 1(PD-L1)-positive tumor cells,ANK therapy is considered effective against adult T-cell lymphoma and malignant lymphoma.CASE SUMMARY Herein,we report a case of an older patient with advanced DLBCL who was successfully treated with ANK immunotherapy.A 91-year-old female visited our hospital with sudden swelling of the right axillary lymph node in April 2022.The patient was diagnosed with stage II disease,given the absence of splenic involvement or contralateral lymphadenopathy.ANK therapy was administered.Six rounds of lymphocyte sampling were performed on July 28,2022.To reduce the occurrence of side effects,the six samples were diluted by half to obtain 12 samples.Cultured NK cells were administered twice weekly.The treatment efficacy was evaluated by performing computed tomography and serological tests every 1 or 2 mo.The treatment suppressed lesion growth,and the antitumor effect persisted for several months.The patient experienced mild side effects.PD-L1 immunostaining was positive,indicating that the treatment was highly effective.CONCLUSION ANK therapy can be used as a first-line treatment for malignant lymphoma;the PD-L1 positivity rate can predict treatment efficacy.

Outcomes of patients treated with SVILE vs.P-GemOx for extranodal natural killer/T-cell lymphoma,nasal type:a prospective,randomized controlled study

Objective:To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma,nasal type(ND-ENKTL).Methods:From April 2015 to July 2018,103 patients with ND-ENKTL were randomly assigned to SVILE(experimental group)or P-GemOx(control group)chemotherapy followed by radiotherapy and consolidation chemotherapy.The primary endpoint was the overall response rate after 3 cycles of chemotherapy,and secondary study endpoints were complete response(CR),progression-free survival(PFS),and overall survival(OS).Safety was also evaluated.Results:There were no significant differences in baseline characteristics in the experimentalvs.control groups.In experimental and control groups,respectively,the overall response rates were 91.7%vs.97.0%for stageI/II and 75.0%vs.72.2%for stage III/IV.The CR rates were 83.4%vs.97.0%for stage I/II and 68.8%vs.61.1%for stage III/IV.None of those differences were significant.There was no significant difference in PFS and OS between groups and between patients in stage I/II and stage III/IV.The 3-year PFS and OS in stage I/II were 88.3%vs.93.3%and 88.8%vs.97.0%,respectively.The 3-year PFS and OS in stage III/IV were 46.2%vs.65.7%and 68.8%vs.72.2%,respectively.The common adverse events were hematological toxicity,hepatotoxicity,and coagulation abnormalities,which were found to be reversible with supportive therapy.Conclusions:The novel SVILE regimen has comparable effects to those of P-GemOx in patients with ND-ENKTL and is well tolerated.SVILE is a therapeutic option for ND-ENKTL.

Muscular involvement of extranodal natural killer/T cell lymphoma misdiagnosed as polymyositis: A case report and review of literature

BACKGROUND Natural killer(NK)/T cell lymphoma is a rare and highly aggressive malignant tumor,and is a special form of non-Hodgkin's lymphoma.Although extranodal involvement is frequently found in tissues such as the skin,testicular and gastrointestinal tract etc,its presence in skeletal muscle has scarcely been reported in the literature.CASE SUMMARY We report a case of extranodal NK/T cell lymphoma with muscle swelling as the first clinical manifestation.A 42-year-old man,who initially presented with localized swelling in the double lower extremities,demonstrated gradual facial and eyelid swelling,and his imaging results showed multiple sites of muscle damage throughout the body.The final pathological results suggested NK/T cell lymphoma,and immunohistochemistry showed CD20(-),CD3(+),CD30(+),CD56(-),EBER(+),Ki67(60%),TIA-1(+)and CD68(±)staining.The muscle swelling significantly improved after treatment with chemotherapy regimens.CONCLUSION This disease is difficult to diagnose and highly invasive,and should be included in the differential diagnosis of unexplained muscle swelling.

Primary intestinal extranodal natural killer/T-cell lymphoma, nasal type: A case report

BACKGROUND Primary intestinal extranodal natural killer/T-cell lymphoma,nasal type(PIENKTCL)is a rare non-Hodgkin’s lymphoma(NHL)subtype,and its prognosis is extremely poor.Clinical characteristics of the disease are not obvious and easily misdiagnosed.In this case report,we describe a patient with PI-ENKTCL who presented with intermittent hematochezia.The advantages of positron emission tomography/computed tomography(PET-CT)as a useful diagnostic tool and the role of surgery as an important therapy are highlighted.CASE SUMMARY A 45-year-old man,hospitalized due to intermittent hematochezia,underwent gastroscopy,colonoscopy,biopsy and CT,but no cause was found.Hence,we carried out a multidisciplinary team(MDT)discussion on the causes and treatment of this patient,and it was decided to perform PET-CT imaging with a MDT discussion of the results.PET-CT demonstrated a diagnosis of lymphoma and it was decided to surgically resect the lesion,and a R0 resection was successfully performed.Postoperative pathology showed negative resection margins,and examination of the lesion confirmed the diagnosis of PI-ENKTCL.After surgery,the patient underwent a follow-up period of 6 mo and received 6 cycles of gemcitabine,oxaliplatin and L-asparaginase.No recurrence or metastasis occurred.CONCLUSION PI-ENKTCL is rare,and MDT discussion is required during diagnosis.PET-CT can be performed for imaging diagnosis.Treatment is based on surgical resection,and the best treatment regimen is determined according to postoperative pathological results to improve prognosis and to extend survival in patients.

Human CD4- CD8- Invariant Natural Killer T Cells Promote IgG Secretion from B Cells Stimulated by Cross-Linking of Their Antigen Receptors

Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4+ CD8β- (CD4) and CD4- CD8β- [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19+CD27- (naïve) and CD19+CD27+ (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.

Combination of atezolizumab and chidamide to maintain long-term remission in refractory metastatic extranodal natural killer/T-cell lymphoma:A case report

BACKGROUND The prognosis of refractory extranodal natural killer/T-cell lymphoma(ENKTL)is poor.Recent data have indicated that immune checkpoint blockade with a programmed cell death protein-1(PD-1)antibody in combination with administration of histone deacetylase inhibitors represents a potentially effective treatment strategy.Compared with PD-1 antibodies,programmed death-ligand 1 antibodies have fewer side effects.Here,we present a rare case of a patient with refractory metastatic ENKTL who achieved sustained remission of approximately 10 mo with minor adverse effects after combination therapy with atezolizumab,chidamide,and radiotherapy.CASE SUMMARY A 56-year-old woman underwent resection of a tumour in her left nasal cavity and was diagnosed with ENKTL(nasal type).Medical examination revealed tumours observed in the bilateral nasal mucosa,the subcutaneous soft tissue of the inner side of the left eye,the soft tissue of the nasopharynx,the bilateral tonsils,and the left preauricular,right hilar,bilateral neck lymph nodes and bone marrow.However,tomography/computed tomography showed increased metabolism of the bilateral nasal mucosa and subcutaneous soft tissue of the inner side of the left eye and newly increased metabolism of the left cervical lymph node after chemotherapy.Therefore,combination therapy with chidamide,atezolizumab,and radiotherapy was performed.Fortunately,the patient achieved a complete response following 10 mo of combination therapy.CONCLUSION The outcome in this case suggests that the combination of atezolizumab,chidamide,and radiotherapy is a promising regimen for treating refractory metastatic ENKTL following chemotherapy treatment failure.

Current status and future perspective of natural killer cell therapy for cancer

Natural killer(NK)cells possess innate abilities to effectively eliminate cancer cells.However,because of difficulties of proliferation and easy to be induced dysfunction in the setting of cancer post NK cell therapy,the curative effect of NK cell infusion has been constrained and not been widely applicable in clinical practice.The rapid development of biotechnology has promoted the development of NK cell therapy for cancer treatment.In this review,we will provide a comprehensive analysis of the current status and future prospects of NK cell therapy for cancer,focusing on the biological characteristics of NK cells,as well as strategies to enhance their targeting capabilities and overcome tumor immune suppression within the microenvironment.

Marine natural product lepadin A as a novel inducer of immunogenic cell death via CD91-dependent pathway

Immunogenic Cell Death(ICD)represents a mechanism of enhancing T cell-driven response against tumor cells.The process is enabled by release of damage-associated molecular patterns(DAMPs)and cytokines by dying cells.Based on molecular studies and clinical marker assessment,ICD can be a new target for cancer chemotherapy hitherto restricted to a few conventional anticancer drugs.In view of the development of small molecules in targeted cancer therapy,we reported the preliminary evidence on the role of the natural product lepadin A(1)as a novel ICD inducer.Here we describe the ICD mechanism of lepadin A(1)by proving the translocation of the protein calreticulin(CRT)to the plasma membrane of human A2058 melanoma cells.CRT exposure is an ICD marker in clinical studies and was associated with the activation of the intrinsic apoptotic pathway in A2058 cells with lepadin A(1).After the treatment,the tumour cells acquired the ability to activate dendritic cells(DCs)with cytokine release and costimulatory molecule expression that is consistent with a phenotypic profile committed to priming T lymphocytes via a CD91-dependent mechanism.The effect of lepadin A(1)was dose-dependent and comparable to the response of the chemotherapy drug doxorubicin(2),a well-established ICD inducer.