Immunobiology最新文献

{"title":"Attenuated S. typhimurium delivery of STAT3-siRNA and endostatin co-expression plasmids for immune and angiogenesis modulation in colorectal cancer","authors":"Ai Cui ,&nbsp;Wenyan Fan ,&nbsp;Tengyi Huang ,&nbsp;Xinyi Li ,&nbsp;Wenjing Xiong ,&nbsp;Yongni Wang ,&nbsp;Yu Chen","doi":"10.1016/j.imbio.2025.153129","DOIUrl":"10.1016/j.imbio.2025.153129","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide. Due to its high metastasis rate and poor prognosis, CRC is the leading cause of cancer-related deaths worldwide.</div></div><div><h3>Materials and methods</h3><div>Combined gene therapy is a promising treatment that can be used to alter the genes involved in cancer genesis and development. This report describes the use of a eukaryotic co-expression plasmid that encodes both STAT3 siRNAs (si-STAT3) and endostatin for the treatment of CRC homografts in C57BL/6 mice, with attenuated <em>Salmonella typhimurium</em> (<em>S. typhimurium</em>) used to facilitate efficient delivery of the plasmid.</div></div><div><h3>Results</h3><div>In this study, single treatment with either si-STAT3 or endostatin showed antitumor effects in the CRC homograft model, and the co-expression treatment had more significant antitumor effects. Not only did the co-expressed plasmids alter the STAT3 and endostatin expression, this treatment also down-regulated MMP2 and cyclin D1 expression and up-regulated caspase 3 expression. The levels of CD4⁺ T cells, CD8⁺ T cells, NK cells, and CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg cells) were also affected by the combined treatment. In addition, the combined therapy altered cytokine expression, enhancing antitumor immunity.</div></div><div><h3>Conclusion</h3><div>The combined gene therapy used in this study additively inhibited colorectal homograft tumor growth.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153129"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis of GINS1 identifies its prognostic and immunotherapy predictive value with in vitro experimental validation in nasopharyngeal carcinoma","authors":"Yang Xu ,&nbsp;Qingqing Zhang ,&nbsp;Wanting Qin ,&nbsp;Zhiyu Yan ,&nbsp;Shuhan Ma ,&nbsp;Yuanyuan Chang ,&nbsp;Kaihua Chen ,&nbsp;Ling Li ,&nbsp;Xiaodong Zhu","doi":"10.1016/j.imbio.2025.153114","DOIUrl":"10.1016/j.imbio.2025.153114","url":null,"abstract":"<div><h3>Background</h3><div>GINS complex subunit 1 (GINS1) is part of the tetrameric GINS complex involved in DNA replication, playing a vital role in controlling the start and continuation of DNA replication. Its role in cancer, however, is not well understood. Still, its relevance to cancer is uncertain. This study focused on exploring the role of GINS1 in different forms of cancer.</div></div><div><h3>Methods</h3><div>Using a range of publicly available databases, we conducted a comprehensive study on the oncogenic function of GINS1 in pan-cancer through analyses of differential expression, survival, enrichment, gene mutations and tumor immune cell infiltration. Additionally, the expression and effects of GINS1 in nasopharyngeal carcinoma (NPC) were analyzed through a series of in vitro experiments.</div></div><div><h3>Results</h3><div>GINS1 was found to be overexpressed in nearly all tumors, demonstrating notable diagnostic and prognostic potential. Moreover, the relationship between GINS1 and specific immune characteristics (such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability) suggests its potential role in guiding immunotherapy approaches. In vitro studies show that GINS1 notably enhances proliferation, migration, and invasion of NPC cells, with elevated expression levels correlating with a poorer prognosis.</div></div><div><h3>Conclusions</h3><div>GINS1 might serve as a prognostic and immunotherapy marker for different types of cancers, such as nasopharyngeal carcinoma.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153114"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sgp130Fc alleviates cartilage degeneration and knee osteoarthritis by inhibiting IL-6 trans-signaling pathway","authors":"Chunrong He ,&nbsp;Lingjie Tan ,&nbsp;Chi Liang ,&nbsp;Jiewen Luo ,&nbsp;Ke Xiao ,&nbsp;Song Wu ,&nbsp;Jinshen He","doi":"10.1016/j.imbio.2025.153122","DOIUrl":"10.1016/j.imbio.2025.153122","url":null,"abstract":"<div><h3>Background</h3><div>Interleukin-6 (IL-6) trans-signaling plays a pivotal role in the pathogenesis and progression of osteoarthritis (OA), contributing to chronic intra-articular inflammation and cartilage degradation. Soluble gp130-Fc (sgp130Fc) is a selective inhibitor of IL-6 trans-signaling that spares classical signaling. This study aimed to elucidate the role of IL-6 trans-signaling in knee OA and evaluate the therapeutic potential of sgp130Fc.</div></div><div><h3>Methods</h3><div>Synovial fluid from OA patients at different disease stages was analyzed for IL-6, soluble IL-6 receptor (sIL-6R), and sgp130 levels by ELISA. Primary rat chondrocytes were treated with Hyper-IL-6 to activate IL-6 trans-signaling and co-treated with sgp130Fc to assess cell viability, gene expression, and lipid metabolism alterations. A rat OA model was established via the Hulth method, followed by intra-articular administration of sgp130Fc. Histological, immunohistochemical, and lipidomic analyses were performed to evaluate cartilage integrity and inflammatory responses.</div></div><div><h3>Results</h3><div>Levels of IL-6, sIL-6R, and sgp130 in synovial fluid increased with OA progression. Hyper-IL-6 impaired chondrocyte viability, activated JAK1-STAT3 signaling, promoted inflammatory and catabolic gene expression, and disrupted lipid metabolism, all of which were reversed by sgp130Fc treatment. In vivo, sgp130Fc injections alleviated cartilage degradation, reduced synovitis, suppressed inflammatory mediators, and restored lipid homeostasis.</div></div><div><h3>Conclusions</h3><div>Targeted inhibition of IL-6 trans-signaling with sgp130Fc effectively mitigates cartilage degeneration and inflammation in OA, highlighting its potential as a novel disease-modifying therapeutic strategy for knee osteoarthritis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153122"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “UMI-77 targets MCL-1 to activate mitophagy and ameliorate periodontitis in mice” [Immunobiology 230(5) (2025) 153108]","authors":"Dalei Sun ,&nbsp;Shu Ouyang ,&nbsp;Xiaoxuan Xu ,&nbsp;Jingjing Yan ,&nbsp;Heqian Wang ,&nbsp;Chenkai Lan ,&nbsp;Wubin Ouyang ,&nbsp;Liangjun Zhong ,&nbsp;Jun Lin","doi":"10.1016/j.imbio.2025.153120","DOIUrl":"10.1016/j.imbio.2025.153120","url":null,"abstract":"","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153120"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changpu Yujin Tang mitigates tourette syndrome by enhancing mitophagy and suppressing NLRP3 inflammasome-mediated pyroptosis","authors":"Shuang Huang ,&nbsp;Liwei Huang ,&nbsp;Mengxue Li ,&nbsp;Mingyang Sun ,&nbsp;Kexin Sun ,&nbsp;Xing Wei ,&nbsp;Bing Jiang ,&nbsp;Yuezhen He ,&nbsp;Fuchun Xue ,&nbsp;Lv Gao ,&nbsp;Manqi Lu ,&nbsp;Jing Shang ,&nbsp;Zhenggang Shi","doi":"10.1016/j.imbio.2025.153118","DOIUrl":"10.1016/j.imbio.2025.153118","url":null,"abstract":"<div><h3>Background</h3><div>Changpu Yujin Tang (CPYJT) is an effective Chinese herbal compound for treating Tourette syndrome (TS). However, its precise molecular mechanisms remain to be fully elucidated.</div></div><div><h3>Methods</h3><div>105 SD rats were randomly divided into the Control (<em>n</em> = 15) and the TS (<em>n</em> = 90) groups. The TS group was induced by intraperitoneal injection of 3,3′-iminodipropionitrile. After successful modeling, the TS group was further divided into 6 subgroups (<em>n</em> = 15 in each group): the Model group, the Tiapride group, the CPYJT group, the Rapamycin (RAPA) group, the 3-methyladenine (3-MA) group, and the CPYJT +3-MA group, and were treated with the corresponding drugs for 4 weeks.</div></div><div><h3>Results</h3><div>Compared with the Control group, rats in the Model group showed increased stereotyped and motor behaviors, damage to striatal neuronal cells and mitochondrial ultrastructure, decreased PINK1/Parkin-mediated mitophagy, and activation of NLRP3 inflammasome. CPYJT reduced stereotyped and motor behaviors, attenuated neuronal cell damage, and repaired mitochondrial pathology in the TS rats. Furthermore, both CPYJT and RAPA enhanced PINK1/Parkin-mediated mitophagy, eliminated ROS accumulation, and inhibited NLRP3 inflammasome activation. Notably, CPYJT counteracted 3-MA's inhibitory effect on PINK1/Parkin-mediated mitophagy, thereby suppressing NLRP3 inflammasome activation and pyroptosis.</div></div><div><h3>Conclusion</h3><div>CPYJT inhibits NLRP3 inflammasome activation and reduces pyroptosis by enhancing PINK1/Parkin-mediated mitophagy and attenuating ROS accumulation, which in turn ameliorates TS.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153118"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Absence of complement terminal pathway activity in C6-deficient mice prolongs survival in a mouse model of severe malarial infection","authors":"Tomoaki Kamiya ,&nbsp;Yuki Miyasaka ,&nbsp;Hangsoo Kim ,&nbsp;Sosuke Fukui ,&nbsp;Masatoshi Inoue ,&nbsp;Masatoshi Ishigami ,&nbsp;Yasuhiro Suzuki ,&nbsp;Shoichi Maruyama ,&nbsp;Tamio Ohno ,&nbsp;Timothy R. Hughes ,&nbsp;B. Paul Morgan ,&nbsp;Masashi Mizuno","doi":"10.1016/j.imbio.2025.153140","DOIUrl":"10.1016/j.imbio.2025.153140","url":null,"abstract":"<div><h3>Background</h3><div>Malaria is an important and serious parasite-induced disease associated with severe anemia and multiple organ failure (MOF) that can be lethal in humans. We explored the contribution of the terminal pathway of complement in a mouse model of malaria-induced lethal MOF following infection with <em>Plasmodium</em> (<em>P.</em>) <em>bergei</em>.</div></div><div><h3>Methods</h3><div>We compared organ damage and survival between C57BL/6 J mice deficient in the terminal pathway component C6 (C6def) and wild type C57BL/6 J mice (WT) after intraperitoneal injection of 10⁶ <em>P. bergei</em>-parasitized erythrocytes. We measured survival, relevant blood parameters, assessed severity of injury and complement activation in relevant organs.</div></div><div><h3>Results</h3><div>All WT mice died between 7 and 13 days after exposure to the parasite challenge; in contrast, C6def mice showed prolonged survival with 80 % alive at day 20, although all then died by day 26. Parasite load and anemia at day 7 were similar in C6def and WT mice. Liver and lung injuries, fibrosis and organ complement deposition assessed at day 7 post-infection were significantly milder in C6def mice compared to WT. Blood platelet count at day 7 post-infection was markedly reduced in WT but not in C6def mice; in contrast, white cell count was increased and hemoglobin levels decreased to similar degrees in WT and C6def mice post-infection. Albumin levels were reduced, significantly more in WT, while blood markers of liver injury were increased, significantly more in WT. Serum levels of complement activation product, C5a, and IL6 were increased in both groups, the latter significantly higher in WT <em>versus</em> C6def mice.</div></div><div><h3>Conclusion</h3><div>We show that complement terminal pathway activation exacerbates organ injuries and thrombocytopenia associated with <em>P. bergei</em> infection, contributing to rapid progression to death in the model. Inhibition of terminal pathway activation in human malarial infections using available drugs might slow progression to organ failure, extending the window of opportunity for the effective use of anti-malarial medicines.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153140"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specific human antibodies against SARS-CoV-2 and monkeypox virus generated via a rapid construction and screening system","authors":"Guanglei Gu ,&nbsp;Jinhai Wang ,&nbsp;Xiaoyun Hu ,&nbsp;Xiuling Gu ,&nbsp;Shirui Li ,&nbsp;Hanle Li ,&nbsp;Min Fang","doi":"10.1016/j.imbio.2025.153124","DOIUrl":"10.1016/j.imbio.2025.153124","url":null,"abstract":"<div><div>Monoclonal antibodies are playing an increasingly important role in modern medicine. Human monoclonal antibodies have become a key focus in the development of monoclonal antibody therapeutics due to their safety. We developed an integrated platform that rapidly constructs and screens human antibodies by combining recombinant antigen production, fluorescent antigen tetramers, memory B-cell sorting, single-cell gene amplification, and single-chain antibody expression for rapid screening of antibody specificity. Using peripheral blood mononuclear cells from healthy donors, we successfully generated human monoclonal antibodies targeting the N and S1 proteins of SARS-CoV-2. Furthermore, we applied the platform to produce protective human antibodies against the M1R protein of the monkeypox virus (MPXV). These results demonstrate that our system enables the rapid and efficient discovery of specific monoclonal antibodies, offering broad applicability for combating emerging infectious diseases and advancing cancer immunotherapies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153124"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual dimorphism in neutrophil function: Unveiling the discriminative nature of male and female neutrophils","authors":"Richard F. Kraus ,&nbsp;Nina Doblinger ,&nbsp;Michael A. Gruber ,&nbsp;Maria S. Wagner ,&nbsp;Johanna Rosenberger","doi":"10.1016/j.imbio.2025.153128","DOIUrl":"10.1016/j.imbio.2025.153128","url":null,"abstract":"<div><h3>Background</h3><div>Women and men are different on many biological levels. Mounting evidence is now recognized that even the immune system has some significant sex differences, which are mainly cell mediated. This study investigated sex-specific differences in function and regulation of polymorphonuclear neutrophil granulocytes (PMNs) in male and female healthy human donors to gain a deeper understanding of the immune response and potential sex-specific dimorphism in immunology.</div></div><div><h3>Methods</h3><div>PMNs were obtained from whole blood samples of healthy female and male donors by leuko−/lymphospin density centrifugation. Chemotaxis assays using μ-slide chemotaxis chambers were performed, in which N-formylmethionin-leucyl-phenylalanine (fMLP) stimulated PMNs migrated through a type I collagen matrix. We measured the production of reactive oxygen species (ROS), the release of myeloperoxidase (MPO), and the formation of Neutrophil Extracellular Traps (NETs). Additionally, a flow cytometry assay was conducted to examine functional variations of neutrophil surface markers CD62L, CD11b, and CD66b, as well as the oxidative burst in PMNs obtained from male and female donors.</div></div><div><h3>Results</h3><div>Sex specific differences of neutrophil function could be determined. Male-derived PMNs initially migrated further distances, while female-derived PMNs showed more targeted movement. However, as the observation period progressed, male-derived PMNs began to exhibit more targeted migration, maintaining straightness towards the end. Differences in neutrophil surface marker expression were observed, with greater levels of CD11b and CD66b on male-derived PMNs after 2 h resting. The different immune effects between the sexes were seen in live cell imaging as well as in flow cytometry analyses.</div></div><div><h3>Conclusion</h3><div>The study revealed significant functional differences between PMNs from male and female donors. To gain reliable results in future PMN studies, it is crucial to consider the sex of the donor.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153128"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATP–NLRP3 inflammasome axis enhances the immunosuppressive effect of myeloid-derived suppressor cells","authors":"Tatsuya Ando ,&nbsp;Kouhei Sakurai ,&nbsp;Masato Hoshi ,&nbsp;Hiroyuki Tezuka ,&nbsp;Yasuhiro Sakai ,&nbsp;Taku Kato ,&nbsp;Hiroyasu Ito","doi":"10.1016/j.imbio.2025.153119","DOIUrl":"10.1016/j.imbio.2025.153119","url":null,"abstract":"<div><div>The effectiveness of immune checkpoint inhibitors is diminished by the presence of myeloid-derived suppressor cells (MDSCs). Recent studies indicate that the NLR family pyrin domain-containing 3 (NLRP3) inflammasome regulates MDSC function, thereby reducing the efficacy of immune checkpoint inhibitors. However, the specific mechanism by which NLRP3 expression induces the immunosuppressive effects in MDSCs remains unclear. Here, we demonstrate that the adenosine triphosphate (ATP)–NLRP3 inflammasome axis enhances the immunosuppressive effects of MDSCs. We found that ATP increases the mRNA levels of immunosuppressive molecules in MDSCs, leading to the suppression of T cell proliferation. Additionally, we showed the efficacy of a novel immune checkpoint therapy that combines an ATP receptor inhibitor (P2X7 receptor inhibitor), an NLRP3 inhibitor, and an anti-PD-L1 antibody (Ab). This combination treatment significantly inhibited tumor growth compared to treatment with only the NLRP3 inhibitor and anti-PD-L1 Ab. These results suggest that the ATP–NLRP3 axis enhances the immunosuppressive effect of MDSCs. In conclusion, this study elucidates the mechanism through which MDSCs acquire immunosuppressive functions, potentially informing the development of novel cancer immunotherapies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153119"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-retroviral treatment of HIV infected individuals improves the ex vivo generation of memory-like NK cells","authors":"Kalavati Lalsare MSc,&nbsp;Shubhangi Bichare MSc,&nbsp;Sheetal Mulay MSc,&nbsp;Rajani D. Bagul MSW,&nbsp;Suvarna Sane M.Phil,&nbsp;Madhuri Thakar PhD","doi":"10.1016/j.imbio.2025.153127","DOIUrl":"10.1016/j.imbio.2025.153127","url":null,"abstract":"<div><div>The ability of Natural Killer (NK) cells, to generate memory-like responses against viruses including – HIV, opened up possibility of their application as immune therapy. We attempted to generate memory-like NK cells from HIV exposed and unexposed primary NK cells. The PBMCs of HIV uninfected and infected individuals (LTNPs, ART experienced and with progressive disease) were preactivated with cytokine cocktail (CC) of IL12, IL 15 and IL 18 with or without HIV-1 Env C or only IL 15 and restimulated with CC + HIV-1 Env C after seven days' rest. The CD56+ NK cells from the cultures were assessed for IFN-γ, TNF-α, and perforin secretion and expression of CD107a using multiparametric flow cytometry. Higher functionality was observed in case of pre-activation with CC with or without HIV-1 Env C as compared to only Il 15 across study groups. However, the functionality of the generated memory -like NK cells was significantly higher in case of LTNPs and the ART experienced individuals only. Low frequency of functional NK cells generated from HIV unexposed NK cells indicate probable specificity to HIV. The memory-like NK cells from ART experienced individuals generated after CC and CC+ HIV-1C preactivation showed good proliferating ability and also an ability to lyse the allogenic HIV infected CD4+ T cells. This work highlighted that HIV specific memory-like NK cells can be generated from the NK cells of HIV infected individuals with robust immune status after pre-activation with cytokine cocktail with or without HIV-1C. Although preliminary, these findings suggest that memory-like NK cells could have potential for use in immunotherapy aimed at clearing viral reservoirs.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153127"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}