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Natural Killer Cell Cytotoxicity:STAT3 Interactions with NF-κB Dimer Composition Modulate Mitochondrial Melatonergic Pathway:Tumor, and Viral Infection Treatment Implications 认领 引用
1
作者 George Anderson 《BIOCELL》 SCIE 2026年第2期23-42,共20页
As natural killer(NK)cells eliminate cancer cells and virus-infected cells,as well as modulate various other medical conditions,including aging-associated conditions such as neurodegenerative disorders,understanding N... As natural killer(NK)cells eliminate cancer cells and virus-infected cells,as well as modulate various other medical conditions,including aging-associated conditions such as neurodegenerative disorders,understanding NK cell regulation is of considerable clinical importance.This article reviews the role of circadian processes(melatonin and the cortisol system),aryl hydrocarbon receptor,and vagal nerve in the modulation of NK cell function,highlighting the importance of the endogenous mitochondrial melatonergic pathway in NK cells.As circadian and exogenous melatonin increase NK cell cytotoxicity,the presence of the endogenous melatonergic pathway may be of some importance not only to NK function and immune checkpoint regulation but also from the efflux of melatonin,which decreases tumor cell survival,proliferation,and metastasis,as well as decreasing immune checkpoint ligands,such as programmed cell ligand 1(PD-L1).NK cell melatonergic pathway regulation may therefore have significant impacts not only on NK cell cytotoxicity but also on the intercellular interactions within tumors and other pathological microenvironments.As melatonin has anti-viral effects,the regulation of the NK cell melatonergic pathway can have wider impacts on how NK cells regulate viral infections,including in the course of viral-induced susceptibility to neurodegenerative conditions.Recent data indicate that the endogenous melatonergic pathway is regulated by interactions of signal transducer and activator of transcription(STAT)3 and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)dimer composition.As both STAT3 and NF-κB dimer composition modulate NK cells,their interaction in the modulation of the NK cell melatonergic pathway will be important to determine.This has significant future research and treatment implications,including improving the clinical efficacy of current treatment approaches such as immune checkpoint inhibition and chimeric antigen receptor(CAR)NK cell therapy,and may accelerate a means of preventing cancer. 展开更多
关键词 Natural killer cells melatonin cancer,viral infection,vagal nerve aryl hydrocarbon receptor treatment aging type 2 diabetes mellitus circadian
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Exploring the Latest Developments in Natural Killer(NK)Cell-Based Therapies for Diffuse Intrinsic Pontine Glioma(DIPG) 认领 引用
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作者 Kawaljit Kaur 《BIOCELL》 SCIE 2026年第3期64-79,共16页
Diffuse intrinsic pontine glioma(DIPG)is a pediatric brainstem tumor with a very poor prognosis,characterized by immunosuppressive tumor microenvironment(TME)that limits immune infiltration,including a significant red... Diffuse intrinsic pontine glioma(DIPG)is a pediatric brainstem tumor with a very poor prognosis,characterized by immunosuppressive tumor microenvironment(TME)that limits immune infiltration,including a significant reduction in circulating natural killer(NK)cells.This drop in NK cell levels and activity may promote tumor growth and immune evasion,making NK cells a promising target for immunotherapy.NK cells can attack and eliminate DIPG tumor cells,including glioma stem cells,while counteracting certain immune evasion strategies.Although theDIPGmicroenvironment and blood-brain barrier present challenges,NKcell-based therapies have shown encouraging tumor control and survival benefits in animal models with promising safety results.Current clinical trials for DIPG mostly focus on chimeric antigen receptor(CAR)-T cells targeting disialoganglioside(GD2)and cluster of differentiation 276(CD276 or B7-H3)antigens with early signs of success,while NK cell therapies,such as CAR-NK cells,are still in preclinical or early stages,requiring further development.The tumor’s immunosuppressive nature poses challenges that may need combination strategies or immune priming.Despite these obstacles,NK cell-based immunotherapy is an exciting and growing field.Upcoming clinical trials emphasize the potential for NK cell therapies to play a critical role in treating this aggressive pediatric brain cancer. 展开更多
关键词 Diffuse intrinsic pontine glioma tumor microenvironment natural killer(NK)cells chimeric antigen receptor(CAR)-NK cells
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Advancements and Challenges of Gamma Delta(γδ)T Cell-and Invariant Natural Killer T(iNKT)Cell-Based Cancer Immunotherapies 认领 引用
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作者 Kawaljit Kaur 《BIOCELL》 SCIE 2026年第2期43-66,共24页
Gamma delta(γδ)T cells and invariant natural killer T(iNKT)cells are unconventional T cells with limited T cell receptor(TCR)diversity.Both can recognize lipid or non-peptide antigens,often through cluster of differ... Gamma delta(γδ)T cells and invariant natural killer T(iNKT)cells are unconventional T cells with limited T cell receptor(TCR)diversity.Both can recognize lipid or non-peptide antigens,often through cluster of differentiation 1d(CD1d),rapidly produce cytokines,express natural killer(NK)cell markers,and are mainly found in mucosal and barrier tissues.Acting as a bridge between innate and adaptive immunity,they show great promise for cancer immunotherapy.DevelopingγδT and iNKT cells for treatment involves shared features like thymic origin,MHC-independent recognition,rapid cytotoxicity,low graft-vs.-host disease(GvHD)risk,ex vivo expansion,and genetic modification,making them suitable for adoptive cell therapies.While their mechanisms are similar,iNKT cells rely on CD1d-mediated antigen presentation,provided by CD1d-expressing antigen-presenting cells(APCs)or engineered cell lines,to activate their invariant TCR and expand effectively.Chimeric antigen receptors(CAR)-induced functional activations make these cell types viable alternatives to conventional cell-based or CAR-T therapies with additional safety benefits.Early clinical trials have shown encouraging results,and their completion will confirm their potential for future treatments.This review explores the biology and mechanisms ofγδT and iNKT cells,focusing on how APCs,cytokines,feeder cells,and CARs contribute to boosting their cytotoxic function,cytokine production,and expansion,enhancing their promise as cancer immunotherapies.It also explores the advancements and challenges in developingγδT and iNKT cell-based immunotherapies,with preclinical and early clinical outcomes offering promising insights. 展开更多
关键词 Gamma delta(γδ)T cells invariant natural killer T(iNKT)cells immunotherapy cancer feeder cells K562 cluster of differentiation 1d(CD1d)molecule
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Arsenic trioxide-induced pyroptosis promotes the release of HMGB1 to activate natural killer cells related immunogenic cell death in leukemia 认领 引用
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作者 Jia-Yin Su Shiyao Song +12 位作者 Zi-Min Song Xi Sun Niangji Tsomo Ying-Li Liu Jingxuan Ma Jie-Si Luo Li-Na Wang Suoyu Xiang Cong Liang Xue-Qun Luo Jun Wu Li-Bin Huang Yan-Lai Tang 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第7期529-535,共7页
The application of Arsenic trioxide(ATO)has greatly improved the cure rates in patients with acute promyelocytic leukemia(APL)and has shown therapeutic effects in other leukemia types,as evidenced by an increasing num... The application of Arsenic trioxide(ATO)has greatly improved the cure rates in patients with acute promyelocytic leukemia(APL)and has shown therapeutic effects in other leukemia types,as evidenced by an increasing number of preclinical trials.However,its clinical application is still limited due to a lack of understanding of the underlying mechanisms.In this report,we have demonstrated that ATO can induce pyroptosis and release damage-associated molecular patterns(DAMPs),such as high mobility group box 1(HMGB1)and interleukin-1β(IL-1β).DAMPs can activate the immunogenic cell death(ICD)mechanism.Our study elucidated the pivotal role of pyroptosis and demonstrated the activation of the caspase-3/gasdermin E(GSDME)pathway both in vivo and in vitro upon ATO intervention.Proteomic analysis of cell supernatants revealed the release of the ICD-associated molecule HMGB1.Results from both in vitro and in vivo experiments collectively demonstrated that the release of HMGB1 is contingent upon GSDME-mediated pyroptosis.Furthermore,label-free quantitative proteomics in vivo indicated that ATO-induced pyroptosis activates natural killer cells(NKs)and promotes the release of granzyme B(GZMB).Our study is the first to demonstrate the synergistic interplay between pyroptosis and ICD mechanisms during ATO treatment,providing novel insights into the potential of ATO for immunotherapy and synergistic treatment approaches. 展开更多
关键词 Arsenic trioxide Pyroptosis Natural killer cells Acute myeloid leukemia Immunogenic cell death
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Tumor microenvironment-driven natural killer cell diversity:mechanisms and therapeutic opportunities 认领 引用
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作者 Yue Duan Mingzhen Zhou +3 位作者 Xingxian Guo Tianyu Cao Yuanyuan Lu Xiaodi Zhao 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第8期1087-1107,共21页
Natural killer(NK)cells are key effector cells involved in tumor immune surveillance,yet their function within the tumor microenvironment(TME)exhibits considerable complexity and plasticity that cannot be adequately e... Natural killer(NK)cells are key effector cells involved in tumor immune surveillance,yet their function within the tumor microenvironment(TME)exhibits considerable complexity and plasticity that cannot be adequately explained by the classical CD56/CD16 dichotomy.This functional diversity arises from the phenotypic adaptability and dynamic differentiation of distinct NK cell subsets shaped by the TME.In this review,we systematically examine the defining characteristics and functional roles of recently identified NK cell subsets in the TME;elucidate the molecular mechanisms governing their regulation;and highlight the functional transitions and cooperative interactions among these subsets.Moreover,building on current evidence,we summarize emerging immunotherapeutic approaches targeting specific NK cell subsets.Together,these perspectives offer new insights and strategic directions for deciphering the multifaceted roles of NK cells in antitumor immunity and advancing the development of subsettargeted therapies. 展开更多
关键词 Tumor microenvironment natural killer cell subsets regulatory mechanism treatment strategies
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Plasma exosomal miR-137 activates natural killer cells in primary biliary cholangitis by targeting NFATC1 认领 引用
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作者 Yi-Fei Yang Qi-Xuan Liu +7 位作者 Wen-Hao Su Bo Zang Bing-Qian Liu Chen-Yang Zhao Yi-Bing Han Ling-Wei Liu Patrick S C Leung Bin Liu 《World Journal of Hepatology》 2026年第6期166-178,共13页
BACKGROUND Primary biliary cholangitis(PBC)is an autoimmune liver disease involving dysregulated natural killer(NK)cell activity.AIM To investigate whether microRNAs(miRNA)modulate NK cell activation and granzyme B se... BACKGROUND Primary biliary cholangitis(PBC)is an autoimmune liver disease involving dysregulated natural killer(NK)cell activity.AIM To investigate whether microRNAs(miRNA)modulate NK cell activation and granzyme B secretion in PBC via the nuclear factor of activated T cell(NFATC)pathway,focusing on the regulatory role of miR-137-3p.METHODS Peripheral blood samples from 168 patients with PBC and 74 healthy controls were analyzed.NK cells were isolated,and miRNA expression was quantified via quantitative polymerase chain reaction.Flow cytometry assessed cluster of differentiation(CD)molecule expression,whereas dual luciferase assays validated miR-137-3p binding to the NFATC1 gene.RESULTS There were significantly lower Ct values(indicating higher expression)for miR-137-3p,miR-124-3p,and miR-506-3p in NK cells from patients with PBC vs cells from healthy controls(all P<0.05).The miR-137-3p directly bound NFATC1,enhancing granzyme B secretion(348.59±7.47 pg/mL vs 373.92±15.50 pg/mL;P<0.05)and increasing the number of CD16+NK cells(73.2%vs 46.8;P<0.05)compared to controls.CONCLUSION Exosomal miR-137-3p promotes NK cell activation in PBC by targeting NFATC1,driving CD16 expression and granzyme B secretion.These miRNAs,particularly miR-137-3p,may serve as novel diagnostic biomarkers or therapeutic targets for PBC. 展开更多
关键词 Primary biliary cholangitis Exosomes MicroRNA-137 Natural killer cells Granzyme B
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Genetically Engineered Natural Killer Cells in Cancer Therapy: Advances, Challenges, and Future Directions 认领 引用
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作者 YOU Yiqi DONG Han XU Jie 《Journal of Shanghai Jiaotong university(Science)》 EI 2026年第3期584-603,I0005,共20页
A cure of cancer remains challenging.With the advancements in gene editing techniques,immune cell-based treatments(e.g.,natural killer(NK)cell therapy)have emerged as potent therapeutic modalities,aiming to address cl... A cure of cancer remains challenging.With the advancements in gene editing techniques,immune cell-based treatments(e.g.,natural killer(NK)cell therapy)have emerged as potent therapeutic modalities,aiming to address clinical bottlenecks associated with traditional approaches.This review recapitulates the inherent characteristics of NK cells as a safe allogeneic tool against cancers,as well as available gene-editing systems for enhancing NK-cell activity,improving persistence,and increasing safety.Furthermore,it summarizes the preclinical and clinical practices of genetically engineered NK cell therapies and highlights their potential,challenges,and future perspectives in cancer treatment.Overall,we provide a comprehensive insight into NK cell-based immunotherapies as a promising approach for cancer treatment. 展开更多
关键词 cancer immunotherapy natural killer(NK)cell genetically engineered NK cell chimeric antigen receptor-engineered NK cell tumor microenvironment
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Exploring the correlation and mechanism of natural killer cell cytotoxic sensitivity against gastric cancer 认领 引用 被引量：1
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作者 WENZHUO YANG HAODONG CHEN +3 位作者 ZHILAN ZHANG ZHIYONG XIA YUANYUAN JIN ZHAOYONG YANG 《Oncology Research》 SCIE 2025年第6期1485-1494,共10页
Background:Human natural killer(NK)cells have attracted widespread attention as a potential adoptive cell therapy(ACT).However,the therapeutic effects of NK cell infusion in patients with solid tumors are limited.Ther... Background:Human natural killer(NK)cells have attracted widespread attention as a potential adoptive cell therapy(ACT).However,the therapeutic effects of NK cell infusion in patients with solid tumors are limited.There is an urgent need to explore a suitable new treatment plan to overcome weaknesses and support the superior therapeutic activity of NK cells.Methods:In this study,the mechanisms underlying the susceptibility of gastric cancer(GC)cell lines AGS,HGC-27,and NCI-N87 to NK cell-mediated cytotoxicity were explored.Results:Lactic dehydrogenase(LDH)release assays showed that all three GC cell lines were susceptible to the umbilical cord blood NK(UCB-NK)cells,and HGC-27 cells with high CD56 expression were the most sensitive to UCB-NK,followed by NCI-N87 and AGS.When the expression of CD56 in HGC-27 cells decreased,the lytic activity of NK cells in HGC-27 cells was abating.In addition,combining oxaliplatin with NK cells produced additive anti-tumor effects in vitro,which may have resulted from oxaliplatin-induced NK group 2 member D(NKG2DL)upregulation in GC cells.These results of cytotoxicity activity showed that inhibition of CD56 expression might suppress the sensitivity of GC cells to NK cell-mediated cytotoxicity,and upregulation of the expression of NKG2DL on the surface of GC cells by oxaliplatin could enhance the killing sensitivity of NK cells.Conclusion:Collectively,our study provides a deeper theoretical foundation and a better therapeutic strategy for NK cell immunotherapy in the treatment of human GC. 展开更多
关键词 Umbilical cord blood natural killer(UCB-NK)cells Oxaliplatin Gastric cancer Natural killer group 2 member D(NKG2D)ligand(NKG2DL) CD56(neural cell adhesion molecule NCAM)
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Natural killer cell dysfunction is associated with colorectal cancer with severe COVID-19 认领 引用
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作者 Jun-Feng Wang Lu-Zhou Zhang +3 位作者 Tao Liu Qing-Hong Meng Jia-Wei Mu Yu-Liang Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2025年第5期327-337,共11页
BACKGROUND Severe acute respiratory syndrome coronavirus 2 induced coronavirus disease 2019(COVID-19)has posed a great challenge to public health worldwide and also increased susceptibility to colorectal cancer(CRC).N... BACKGROUND Severe acute respiratory syndrome coronavirus 2 induced coronavirus disease 2019(COVID-19)has posed a great challenge to public health worldwide and also increased susceptibility to colorectal cancer(CRC).Natural killer(NK)cells serve as the first line of defense in the host’s innate immune system,performing natural killing functions and mediating cytotoxicity against tumors and viruses.Therefore,a better understanding of NK cell cytotoxicity may facilitate the development of treatment strategies for CRC-associated with COVID-19.AIM To investigate the cytotoxic killing function of peripheral NK cells in patients with CRC and severe COVID-19(CRC+patients).METHODS The percentages of circulating NK and NKT cells in CRC+and age-matched patients with CRC were analyzed using flow cytometry.NK cell cytotoxic activity(NKCA)and corresponding NK cytotoxic factor(NKCF)activity in peripheral blood mononuclear cells were evaluated using a Real-Time Cell Analyzer.RESULTS The numbers and percentage of peripheral NK and NKT cells in patients with CRC+were lower than those in patients with CRC.Additionally,compared to patients with CRC,those with CRC+had lower levels of NKCA and NKCF activity in lysed K562 cells.Positive correlations were observed between NKCA and NK cell numbers,NKCA and NK cell percentages,NKCF activity,and NK cell percentages in patients with CRC+.Furthermore,a negative correlation was observed between NKCA and the severity of COVID-19 in patients with CRC.The area under the receiver operating characteristic curve for NKCA was greater than those for the other indices.CONCLUSION CRC+is associated with lower levels of peripheral NK cells and impaired natural cytotoxicity,contributing to the immunopathogenesis of severe COVID-19 rather than immune control. 展开更多
关键词 Colorectal cancer COVID-19 Natural killer cells Natural cytotoxicity Natural killer cytotoxic factor
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High-risk extranodal natural killer/T-cell lymphoma patients could benefit more from allogeneic hematopoietic stem cell transplantation as consolidation:A real-world multicenter analysis in China 认领 引用
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作者 Yuewen Wang Yi Xia +18 位作者 Zhenyang Gu Yu Chang Lei Yang Peipei Yang Yanmin Zhao Chunli Zhang Na Wang Shenmiao Yang Yang Yang Chuanhe Jiang Leqing Cao Daoxing Deng Haiyang Lu Fengrong Wang Mingzhi Zhang Yang Cao Xiaoxia Hu Ting Niu Xiaodong Mo 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2025年第5期686-704,共19页
Objective:Both allogeneic hematopoietic stem cell transplantation(allo-HSCT)and autologous HSCT(ASCT)are important therapies for extranodal natural killer/T-cell lymphoma(ENKTCL);however,no large-scale,multicenter stu... Objective:Both allogeneic hematopoietic stem cell transplantation(allo-HSCT)and autologous HSCT(ASCT)are important therapies for extranodal natural killer/T-cell lymphoma(ENKTCL);however,no large-scale,multicenter study has compared the efficacy and safety between allo-HSCT and ASCT in these patients.Our multicenter,real-world study aimed to evaluate the outcomes of allo-HSCT vs.ASCT as consolidation in ENKTCL patients who had achieved a complete response(CR)or partial response(PR).Methods:This was a multicenter,retrospective study with nine hospitals in China,and 114 patients with ENKTCL were enrolled.Sixty patients received ASCT and 54 received allo-HSCT.The primary outcome was progression-free survival(PFS).In the sensitivity analysis,propensity score matching(PSM)analyses were conducted to adjust for baseline prognostic factors.Landmark analysis were conducted to minimize immortal-time bias.Results:Patients in the allo-HSCT group presented with more adverse prognostic factors.Allo-HSCT group showed a significantly better PFS and a lower disease progression rate compared with ASCT group in patients with Ann Arbor stageⅢ/Ⅳdisease(PFS:100%vs.82.0%,P=0.023;disease progression rate:0 vs.25.4%,P=0.024),those with intermediate/high prognostic index of natural killer lymphoma(PINK)scores(PFS:100%vs.84.4%,P=0.034;disease progression rate:0 vs.22.1%,P=0.034),those with intermediate/high international prognostic index(IPI)scores(PFS:100%vs.82.0%,P=0.038;disease progression rate:0 vs.25.4%,P=0.038),or those receiving HSCT at PR(PFS:100%vs.50%,P=0.046;disease progression rate:0 vs.50%,P=0.046)at the 1.5-4.0 follow-up.In multivariate analysis,receiving ASCT was significantly associated with a poorer PFS[hazard ratio(HR)=2.23,P=0.038]and overall survival(OS)(HR=2.45,P=0.045).In the sensitivity analysis,patients receiving allo-HSCT showed a significantly better PFS(70.3%vs.39.1%,P=0.039),OS(73.9%vs.42.0%,P=0.044),and a lower disease progression rate(22.6%vs.57.0%,P=0.017)compared with those receiving ASCT after propensity score matching.Conclusions:ENKTCL patients with high-risk characteristics could benefit more from allo-HSCT as consolidation. 展开更多
关键词 Extranodal natural killer/T-cell lymphoma allogeneic hematopoietic stem cell transplantation autologous hematopoietic stem cell transplantation consolidation therapy high-risk disease
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In Vitro and Animal Studies of Human Natural Killer Cell-Derived Exosomes for the Treatment of Otitis Media 认领 引用
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作者 Zirui Zhao Liqin Wang +7 位作者 Zhen Guo Kanglun Jiang Jianghong Xu Yilai Shu Christina Y.Xu Jianning Zhang Yunfeng Wang Geng-Lin Li 《Neuroscience Bulletin》 SCIE CAS CSCD 2025年第10期1792-1804,共13页
Otitis media is an infection of the middle ear mainly caused by bacteria,and current treatments rely heavily on antibiotics.However,the emergence of antibiotic-resistant bacterial strains seriously affects their effic... Otitis media is an infection of the middle ear mainly caused by bacteria,and current treatments rely heavily on antibiotics.However,the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy.In our study,we found that extracellular vesicles(EVs)derived from human natural killer cells(NKs)inhibit the proliferation of both standard and levofloxacin(LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner.Moreover,compared to LVX,EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models.For LVX-sensitive strains,EVs were significantly more effective in terms of curative time but not curative rate.For LVX-resistant strains,EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX.In summary,we found that NK EVs are highly effective in treating otitis media,providing an alternative approach for treating this common disease. 展开更多
关键词 Natural killer cell Extracellular vesicle Otitis media Anti-bacteria
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Natural killer cell-based immunotherapies for colorectal cancer:Current strategies,challenges,and future perspectives 认领 引用
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作者 Xiao-Jun Zhang Yan Yu +9 位作者 Jing-Yu Li Yu-Zhu Yan Sha-Sha Jiang Yi Zhang Qin Fei Yi-Ran Zhang Yong-Xin Zhao Lei Guo Jing Lv He-Ping Zhao 《World Journal of Gastroenterology》 SCIE CAS 2025年第34期11-30,共20页
Natural killer(NK)cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization.In this review,NK ... Natural killer(NK)cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization.In this review,NK cell-based immunotherapeutic approaches,including cytokine therapy,immune checkpoint inhibition,antibody-dependent cellular cytotoxicity,and adoptive cell transfer,are comprehensively examined,and their respective clinical potential and limitations are highlighted.We discuss critical challenges in NK cell expansion,genetic engineering(particularly chimeric antigen receptor-NK development),and tumor microenvironment-mediated immunosuppression.Furthermore,we explore innovative strategies such as combination therapies,nanotechnology-enhanced delivery,and personalized medicine approaches that aim to overcome the current barriers.The review concludes with future directions emphasizing the need for standardized manufacturing protocols,new strategies to improve NK cell persistence,and clinical validation of emerging technologies,positioning NK cell immunotherapy as a transformative modality for colorectal cancer treatment. 展开更多
关键词 Natural killer cells Colorectal cancer Immunotherapy Immunosuppression Tumor microenvironment
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Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer 认领 引用
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作者 SHIQIN JIANG YICHUN TANG +2 位作者 FENG MA YUCHUN NIU LEI SUN 《Oncology Research》 SCIE 2025年第1期213-224,共12页
Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limite... Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy. 展开更多
关键词 Ubiquitin-specific protease 1(USP1) Natural killer(NK)cell Small cell lung cancer(SCLC) Prognosis Immune escape
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Chimeric antigen receptor-natural killer cell therapy:A new force in intrinsic immunotherapy for cancer 认领 引用
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作者 Zhen-Ni ChenLiu Lei-Han Wang Dong Tang 《Journal of Nutritional Oncology》 2025年第3期69-78,共10页
Revolutionary breakthroughs in tumor treatment have been achieved through the rapid progress of cancer immunotherapy,notably through the clinical promise shown by chimeric antigen receptor(CAR)–modified immune cell th... Revolutionary breakthroughs in tumor treatment have been achieved through the rapid progress of cancer immunotherapy,notably through the clinical promise shown by chimeric antigen receptor(CAR)–modified immune cell therapies.Compared with traditional CAR-T cell therapy,CAR-natural killer(NK)cell therapy has become an emergingfield in tumor immunotherapy due to its unique innate immune advantages:(1)it can kill tumors through natural cytotoxicity mechanisms without major histocompatibility com-plexes restricted recognition,(2)the rich activating receptors provide multiple tumor recognition pathways,and(3)the lower risk of cytokine release syndrome endows it with better safety characteristics.Efforts include refining target antigens such as CD19 and natural killer group 2D ligands,designing novel costimulatory domains like DNAX accessory molecule-1 and 2B4,and developing universal allogeneic treatment platforms.However,the technology still faces key challenges:insufficient in vivo persistence,sup-pression by the tumor microenvironment,low transduction efficiency,and the standardization of large-scale production processes are urgent problems to be solved.This review aims to systematically examine how CAR-NK cells exert their effects,summarize the latest breakthroughs in clinical and technicalfields,and explore existing scientific challenges as well as potential approaches to address them.The insights offered aim to inform future directions in CAR-NK cell research and development. 展开更多
关键词 Cancer CAR-NK cells in cancer Natural killer cell in cancer Newest cell therapy
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Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon 认领 引用 被引量：2
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作者 Nada M Melhem Rami A Mahfouz +5 位作者 Khalil Kreidieh Rabab Abdul-Khalik Rolla El-Khatib Reem Talhouk Umayya Musharrafieh Ghassan Hamadeh 《World Journal of Hepatology》 2016年第29期1212-1221,共10页
AIMTo explore the role of killer immunoglobulin receptor (KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus. METHODSWe recruited 101 voluntary participants between March 2010 ... AIMTo explore the role of killer immunoglobulin receptor (KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus. METHODSWe recruited 101 voluntary participants between March 2010 and December 2011. Sera samples from vaccinated and non-vaccinated participants were tested for the presence of anti-HBs antibodies as a measure of protection against hepatitis B, hepatitis B surface antigen and hepatitis B core antibody as indicators of infection by enzyme-linked immunosorbent assay. KIR gene frequencies were determined by polymerase chain reaction. RESULTSSera samples from 99 participants were tested for the levels of anti-HBs as an indicator of protection (&ge; 10 mIU/mL) following vaccination as defined by the World Health Organization international reference standard. Among the vaccinated participants, 47% (35/74) had anti-HBs titers above 100 mIU/mL, 22% (16/74) had anti-HBs ranging between 10-100 mIU/mL, and 20% (15/74) had values of less than 10 mIU/mL. We report the lack of significant association between the number of vaccine dosages and the titer of antibodies among our vaccinated participants. The inhibitory KIR2DL1, KIR2DL4, KIR3DL1, KIR3DL2, and KIR3DL were detected in more than 95%, whereas KIR2DL2, KIR2DL3, KIR2DL5 (KR2DL5A and KIR2DL5B) were expressed in 56%, 84% and 42% (25% and 29%) of participants, respectively. The observed frequency of the activating KIR genes ranged between 35% and 55% except for KIR2DS4, detected in 95% of the study participants (40.6% 2DS4*001/002; 82.2% 2DS4*003/007). KIR2DP1 pseudogene was detected in 99% of our participants, whereas KIR3DP*001/02/04 and KIR3DP1*003 had frequencies of 17% and 100%, respectively. No association between the frequency of KIR genes and anti-HBs antibodies was detected. When we compared the frequency of KIR genes between vaccinated individuals with protective antibodies titers and those who lost their protective antibody levels, we did not detect a significant difference. KIR2DL5B was significantly different among different groups of vaccinated participants (group I > 100 mIU/mL, group II 10-100 mIU/mL, group III CONCLUSIONTo our knowledge, this is the first study screening for the possible role of KIR genes among individuals vaccinated against hepatitis B virus (HBV). Our results can be used to design larger studies to better understand the role of KIR genes in protection against or susceptibility to HBV post vaccination. 展开更多
关键词 Hepatitis B virus Killer immunoglobulin receptors Hepatitis B vaccine Lebanon Natural killer cells
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Role natural killer group 2D-ligand interactions in hepatitis B infection 认领 引用 被引量：5
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作者 Teresa Pollicino Lemonica Koumbi 《World Journal of Hepatology》 2015年第6期819-824,共6页
Hepatitis B virus （HBV） infection is the leading causeof liver disease and hepatocellular carcinoma （HCC）worldwide, in spite of prophylactic vaccination andantiviral treatment modalities. The immunopathogenesisof ... Hepatitis B virus （HBV） infection is the leading causeof liver disease and hepatocellular carcinoma （HCC）worldwide, in spite of prophylactic vaccination andantiviral treatment modalities. The immunopathogenesisof HBV infection has been intensively studied and ispropelled by complex interactions between the virus andthe host immune system. Natural killer group 2D （NKG2D）is a well-characterized activating receptor, expressed onnatural killer （NK） cells, NK T cells and CD8＋ cytotoxic Tcells. This receptor is present in both humans and miceand binds to a diverge family of ligands that resemble theMHC-class Ⅰ molecules. Increasing evidence shows thatNKG2D-ligand interactions are critical in the establishmentof HBV persistence and the development of liver injuryand HCC. The expression of NKG2D ligands dependson the presence of several polymorphisms and is alsomodulated post-transcriptionally by HBV. While it isknown that HBV circumvents host’s innate immunityvia the NKG2D pathway but the exact mechanismsinvolved are still elusive. This letter discusses previousaccomplishments on the role of NKG2D ligand regulationin the development of chronic HBV, liver injury and HCC.Key words： Hepatitis B virus; Natural killer group 2Dreceptor; Natural killer cells; MHC class I polypeptiderelatedchain A; Hepatocellular carcinoma 展开更多
关键词 Hepatitis B virus Natural killer group 2Dreceptor Natural killer cells MHC class I polypeptiderelatedchain A Hepatocellular carcinoma
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Isolation and identification of a marine killer yeast strain YF07b and cloning of the gene encoding killer toxin from the yeast 认领 引用 被引量：1
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作者 WANG Xianghong CHI Zhenming LI Jing 《Acta Oceanologica Sinica》 SCIE CAS 2007年第6期101-108,共8页
It was found that the marine yeast strain YF07b could secrete a large amount of killer toxin against a pathogenic yeast strain WCY which could cause milky disease in Portunus trituberculcttus.The marine yeast strain Y... It was found that the marine yeast strain YF07b could secrete a large amount of killer toxin against a pathogenic yeast strain WCY which could cause milky disease in Portunus trituberculcttus.The marine yeast strain YF07b was identified to be Pichia anomala according to the results of routine yeast identification and 18S rDNA and ITS sequences.The gene encoding killer toxin in the marine yeast strain YF07b was amplified by PCR technology.After sequencing,the results show that an open reading frame,consisting of 1281 bp,encoded a presumed protein of 427 amino acids.The sequence of the cloned gene was found to have 99%match with that of the gene encoding killer toxin in Pichia anomalas strain K.A signal peptide including 17 amino acids appeared in the N-terminal domain of the killer toxin.Therefore,the mature protein consisted of 410 amino acids,its molecular mass was estimated to be 47.4 ku and its isoelctronic point was 4.5. 展开更多
关键词 pathogenic yeast crab marine killer yeast identification killer toxin gene cloning
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Intrahepatic natural killer T cell populations are increased in human hepatic steatosis 认领 引用 被引量：13
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作者 Michael Adler Sarah Taylor +4 位作者 Kamalu Okebugwu Herman Yee Christine Fielding George Fielding Michael Poles 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第13期1725-1731,共7页
AIM: To determine if natural killer T cell (NKT) populations are affected in nonalcoholic fatty liver disease (NAFLD). METHODS: Patients undergoing bariatric surgery underwent liver biopsy and blood sampling during su... AIM: To determine if natural killer T cell (NKT) populations are affected in nonalcoholic fatty liver disease (NAFLD). METHODS: Patients undergoing bariatric surgery underwent liver biopsy and blood sampling during surgery. The biopsy was assessed for steatosis and immunocyte infiltration. Intrahepatic lymphocytes (IHLs) were isolated from the remainder of the liver biopsy, and peripheral blood mononuclear cells (PBMCs) were isolated from the blood. Expression of surface proteins on both IHLs and PBMCs were quantified using flow cytometry. RESULTS: Twenty-seven subjects participated in thisstudy. Subjects with moderate or severe steatosis had a higher percentage of intrahepatic CD3+/CD56+ NKT cells (38.6%) than did patients with mild steatosis (24.1%, P = 0.05) or those without steatosis (21.5%, P = 0.03). Patients with moderate to severe steatosis also had a higher percentage of NKT cells in the blood (12.3%) as compared to patients with mild steatosis (2.5% P = 0.02) and those without steatosis (5.1%, P = 0.05). CONCLUSION: NKT cells are significantly increased in the liver and blood of patients with moderate to severe steatosis and support the role of NKT cells in NAFLD. 展开更多
关键词 Nonalcoholic fatty liver disease Natural killer T cells Natural killer T-like cells Lymphocytes Hepatic steatosis
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The effects of stereotactic body radiotherapy on peripheral natural killer and CD3~+CD56~+ NKT-like cells in patients with hepatocellular carcinoma 认领 引用 被引量：1
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作者 Tian-Tian Li Jing Sun +4 位作者 Quan Wang Wen-Gang Li Wei-Ping He Rui-Chuang Yang Xue-Zhang Duan 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2021年第3期240-250,共11页
Background: Both natural killer(NK) and CD3+CD56+ natural killer T(NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy(SBRT) on peri... Background: Both natural killer(NK) and CD3+CD56+ natural killer T(NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy(SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma(HCC), and to identify possible surface markers on these cells that correlate with the prognosis. Methods: Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γand TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. Results: The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+ NK cells before SBRT and higher percentage of CD158b + NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. Conclusions: SBRT has an apparent effect on both peripheral NK and CD3+ CD56+ NKT-like cells. Lower percentage of NKp30 + NK cells before SBRT and higher percentage of CD158b + NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+ CD56+ NKT-like cells is associated with higher OS in HCC patients. 展开更多
关键词 Nature killer cells Hepatocellular carcinoma Nature killer T-like cells Stereotactic body radiotherapy
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Effects of acupuncture treatment on natural killer cell activity,pulse rate,and pain reduction for older adults:an uncontrolled,observational study 认领 引用 被引量：10
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作者 Hidetoshi Mori Hiroshi Kuge +3 位作者 Tim Hideaki Tanaka Eiichi Taniwaki Kazuyo Hanyu Tateyuki Morisawa 《Journal of Integrative Medicine》 CAS CSCD 2013年第2期101-105,共5页
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 indivi... 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. 展开更多
关键词 acupuncture therapy killer cells, natural leukocytes heart rate pain measurement clinical trial
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