{"title":"A Sampling of Highlights from the Literature.","authors":"","doi":"10.1158/2326-6066.CIR-12-12-WWR","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-12-12-WWR","url":null,"abstract":"","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"12 12","pages":"1661"},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne-Charlotte Le Floch, Caroline Imbert, Nicolas Boucherit, Laurent Gorvel, Stéphane Fattori, Florence Orlanducci, Aude Le Roy, Lorenzo Archetti, Lydie Crescence, Laurence Panicot-Dubois, Christophe Dubois, Norbert Vey, Antoine Briantais, Amandine Anastasio, Carla Cano, Geoffrey Guittard, Mathieu Frechin, Daniel Olive
{"title":"Targeting BTN2A1 Enhances Vγ9Vδ2 T-Cell Effector Functions and Triggers Tumor Cell Pyroptosis.","authors":"Anne-Charlotte Le Floch, Caroline Imbert, Nicolas Boucherit, Laurent Gorvel, Stéphane Fattori, Florence Orlanducci, Aude Le Roy, Lorenzo Archetti, Lydie Crescence, Laurence Panicot-Dubois, Christophe Dubois, Norbert Vey, Antoine Briantais, Amandine Anastasio, Carla Cano, Geoffrey Guittard, Mathieu Frechin, Daniel Olive","doi":"10.1158/2326-6066.CIR-23-0868","DOIUrl":"10.1158/2326-6066.CIR-23-0868","url":null,"abstract":"<p><p>Vγ9Vδ2 T cells are potent but elusive cytotoxic effectors. Butyrophilin subfamily 2 member A1 (BTN2A1) is a surface protein that has recently been shown to bind the Vγ9 chain of the γδ T-cell receptor, but its precise role in modulating Vγ9Vδ2 T-cell functions remains unknown. Here, we show that 107G3B5, a monoclonal BTN2A1 agonist antibody, was able to significantly enhance Vγ9Vδ2 T-cell functions against hematologic or solid cell lines and against primary cells from patients with adult acute lymphoblastic leukemia. New computer vision strategies applied to holotomographic microscopy videos showed that 107G3B5 enhanced the interaction between Vγ9Vδ2 T cells and target cells in a quantitative and qualitative manner. In addition, we found that Vγ9Vδ2 T cells activated by 107G3B5 induced caspase 3/7 activation in tumor cells, thereby triggering tumor cell death by pyroptosis. Together, these data demonstrate that targeting BTN2A1 with 107G3B5 enhances the Vγ9Vδ2 T-cell antitumor response by triggering pyroptosis-induced immunogenic cell death. These new pyroptosis-based therapies have great potential to stimulate the immune system to fight cancer, especially \"cold\" tumors. See related Spotlight by Kabelit, p. 1662.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1677-1690"},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin C Boucher, Gongbo Li, Hiroshi Kotani, Maria L Cabral, Dylan Morrissey, Sae Bom Lee, Kristen Spitler, Nolan J Beatty, Estelle V Cervantes, Bishwas Shrestha, Bin Yu, Aslamuzzaman Kazi, Xuefeng Wang, Said M Sebti, Marco L Davila
{"title":"Correction: CD28 Costimulatory Domain-Targeted Mutations Enhance Chimeric Antigen Receptor T-cell Function.","authors":"Justin C Boucher, Gongbo Li, Hiroshi Kotani, Maria L Cabral, Dylan Morrissey, Sae Bom Lee, Kristen Spitler, Nolan J Beatty, Estelle V Cervantes, Bishwas Shrestha, Bin Yu, Aslamuzzaman Kazi, Xuefeng Wang, Said M Sebti, Marco L Davila","doi":"10.1158/2326-6066.CIR-24-1029","DOIUrl":"10.1158/2326-6066.CIR-24-1029","url":null,"abstract":"","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1808"},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yushen Du, Ramin Salehi-Rad, Tian-Hao Zhang, William P Crosson, Jensen Abascal, Dongdong Chen, Yuan Shi, Hong Jiang, Yen-Wen Tseng, Xi Ma, Mengying Hong, Sihan Wang, Xijuan Wang, Kejun Tang, Shiyao Hu, Yuting Li, Shaokai Ni, Yiqi Cai, Shahed Tappuni, Yong Shen, Bin Liu, Ren Sun
{"title":"Hyper-Interferon Sensitive Influenza Induces Adaptive Immune Responses and Overcomes Resistance to Anti-PD-1 in Murine Non-Small Cell Lung Cancer.","authors":"Yushen Du, Ramin Salehi-Rad, Tian-Hao Zhang, William P Crosson, Jensen Abascal, Dongdong Chen, Yuan Shi, Hong Jiang, Yen-Wen Tseng, Xi Ma, Mengying Hong, Sihan Wang, Xijuan Wang, Kejun Tang, Shiyao Hu, Yuting Li, Shaokai Ni, Yiqi Cai, Shahed Tappuni, Yong Shen, Bin Liu, Ren Sun","doi":"10.1158/2326-6066.CIR-23-1075","DOIUrl":"10.1158/2326-6066.CIR-23-1075","url":null,"abstract":"<p><p>Despite recent advances in immunotherapy with immune checkpoint inhibitors, many patients with non-small cell lung cancer (NSCLC) fail to respond or develop resistance after an initial response. In situ vaccination (ISV) with engineered viruses has emerged as a promising antigen-agnostic strategy that can both condition the tumor microenvironment and augment antitumor T-cell responses to overcome immune resistance. We engineered a live attenuated viral vaccine, hyper-IFN-sensitive (HIS) virus, by conducting a genome-wide functional screening and introducing eight IFN-sensitive mutations in the influenza genome to enhance host IFN response. Compared with wild-type influenza, HIS replication was attenuated in immunocompetent hosts, enhancing its potential as a safe option for cancer therapy. HIS ISV elicited robust yet transient type I IFN responses in murine NSCLCs, leading to an enrichment of polyfunctional effector Th1 CD4+ T cells and cytotoxic CD8+ T cells into the tumor. HIS ISV demonstrated enhanced antitumor efficacy compared with wild-type in multiple syngeneic murine models of NSCLC with distinct driver mutations and varying mutational burden. This efficacy was dependent on host type 1 IFN responses and T lymphocytes. HIS ISV overcame resistance to anti-PD-1 in LKB1-deficient murine NSCLC, resulting in improved overall survival and systemic tumor-specific immunity. These studies provide compelling evidence to support further clinical evaluation of HIS as an \"off-the-shelf\" ISV strategy for patients with NSCLC refractory to immune checkpoint inhibitors.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1765-1779"},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen Zhang, Xuan Zhao, Qitai Zhao, Xinfeng Chen, Congcong Li, Yaqing Liu, Chunyi Shen, Lijie Song, Lijun Miao, Fuyou Guo, Xiaoning Mou, Jie Zhao, Weiyue Gu, Yi Zhang
{"title":"Peripheral Blood-Derived PD-1/CD28-CD19 CAR-Modified PD-1+ T-Cell Therapy in Patients with Solid Tumors.","authors":"Zhen Zhang, Xuan Zhao, Qitai Zhao, Xinfeng Chen, Congcong Li, Yaqing Liu, Chunyi Shen, Lijie Song, Lijun Miao, Fuyou Guo, Xiaoning Mou, Jie Zhao, Weiyue Gu, Yi Zhang","doi":"10.1158/2326-6066.CIR-24-0037","DOIUrl":"10.1158/2326-6066.CIR-24-0037","url":null,"abstract":"<p><p>T cells expressing programmed cell death 1 (PD-1) in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD-1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1- T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T-cell activation-related pathways compared with PD-1- T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity toward autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1/CD28 fusion receptor combined with a CD19 chimeric antigen receptor into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1/CD28-CD19 chimeric antigen receptor PD-1+ T cells. None of these patients experienced severe side effects, and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for patients with cancer.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1703-1717"},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment.","authors":"Ayaka Tsuge, Sho Watanabe, Akihito Kawazoe, Yosuke Togashi, Kota Itahashi, Mari Masuda, Atsuo Sai, Shogo Takei, Hiromi Muraoka, Shuichi Ohkubo, Daisuke Sugiyama, Yue Yan, Shota Fukuoka, Toshihiko Doi, Kohei Shitara, Shohei Koyama, Hiroyoshi Nishikawa","doi":"10.1158/2326-6066.CIR-24-0713","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0713","url":null,"abstract":"<p><p>Regulatory T (Treg) cells play key roles in cancer immunity by suppressing a range of antitumor immune responses and contributing to resistance to programmed death (PD)-1 blockade therapy. Given their critical roles in self-tolerance, local control of immunosuppression by Treg cells, such as in the tumor microenvironment (TME), has been intensively studied. Inhibition of heat shock protein 90 (HSP90), a chaperone with vital roles in regulating proteostasis in cancer cells, impedes cancer progression by interrupting oncogenic signaling pathways and potentially modulating antitumor immunity, but we have very little mechanistic insight into these immune modulatory effects. Here, we show that the number of Treg cells are selectively reduced by the HSP90 inhibitor pimitespib in animal models and patients with gastric cancer in a clinical trial (EPOC1704). Pimitespib reduced the highly immunosuppressive human FOXP3high effector Treg cells by inhibiting their proliferation and decreasing their expression of effector molecules, which improved the priming and activation of antigen-specific CD8+ T cells. Mechanistic studies revealed that pimitespib selectively degraded STAT5, a key transducer of the IL-2 signaling pathway, which is essential for Treg cell development and maintenance, and consequently compromised FOXP3 expression, leading to selective impairment of immunosuppression in the TME by Treg cells. Thus, pimitespib treatment combined with PD-1 blockade exhibited a far stronger antitumor effect than either treatment alone in animal models. Through these data, we propose that HSP90 inhibition is a promising therapeutic option for Treg cell-targeted cancer immunotherapy.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blocking WNT7A Enhances MHC-I Antigen Presentation and Enhances the Effectiveness of Immune Checkpoint Blockade Therapy.","authors":"Jiazheng Sun, Pin Wang, Ziying Yi, Yushen Wu, Yuxian Wei, Huiying Fang, Daqiang Song, Yuru Chen, Huimin Du, Jing Huang, Qin Li, Dejuan Yang, Guosheng Ren, Hongzhong Li","doi":"10.1158/2326-6066.CIR-24-0484","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0484","url":null,"abstract":"<p><p>The limited infiltration of CD8+ T cells in tumors hampers the effectiveness of T cell-based immunotherapy, yet the mechanisms that limit tumor infiltration by CD8+ T cells remain unclear. Through bulk RNA sequencing of human tumors, we identified a strong correlation between WNT7A expression and reduced CD8+ T-cell infiltration. Further investigation demonstrated that inhibiting WNT7A substantially enhanced MHC-I expression on tumor cells. Mechanistically, WNT7A inhibition inactivated Wnt/β-catenin signaling pathway and thus resulted in reduced physical interaction between β-catenin and p65 in the cytoplasm, which increased the nuclear translocation of p65 and activated the NF-κB pathway, ultimately promoting the transcription of genes encoding MHC-I molecules. We found that our lead compound, 1365-0109, disrupted the protein-protein interaction between WNT7A and its receptor FZD5, resulting in the upregulation of MHC-I expression. In murine tumor models, both genetic and pharmaceutical suppression of WNT7A led to increased MHC-I levels on tumor cells, and consequently enhanced the infiltration and functionality of CD8+ T cells, which bolstered antitumor immunity and improved the effectiveness of immune checkpoint blockade therapy. These findings have elucidated the intrinsic mechanisms of WNT7A-induced immune suppression, suggesting that therapeutic interventions targeting WNT7A hold promise for enhancing the efficacy of immunotherapy.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meaghan K McGeary, William Damsky, Andrew J Daniels, Sabine M Lang, Qingji Xu, Eric Song, Clotilde Huet-Calderwood, Hua Jane Lou, Sateja Paradkar, Goran Micevic, Susan M Kaech, David A Calderwood, Benjamin E Turk, Qin Yan, Akiko Iwasaki, Marcus W Bosenberg
{"title":"Setdb1-loss induces type-I interferons and immune clearance of melanoma.","authors":"Meaghan K McGeary, William Damsky, Andrew J Daniels, Sabine M Lang, Qingji Xu, Eric Song, Clotilde Huet-Calderwood, Hua Jane Lou, Sateja Paradkar, Goran Micevic, Susan M Kaech, David A Calderwood, Benjamin E Turk, Qin Yan, Akiko Iwasaki, Marcus W Bosenberg","doi":"10.1158/2326-6066.CIR-23-0514","DOIUrl":"10.1158/2326-6066.CIR-23-0514","url":null,"abstract":"<p><p>Despite recent advances in the treatment of melanoma, many patients with metastatic disease still succumb to their disease. To identify tumor-intrinsic modulators of immunity to melanoma, we performed a whole-genome CRISPR screen in melanoma and identified Setdb1 as well as all components of the HUSH complex. We found that loss of Setdb1 leads to increased immunogenicity and complete tumor clearance in a CD8+ T-cell dependent manner. Mechanistically, loss of Setdb1 causes de-repression of endogenous retroviruses (ERVs) in melanoma cells and triggers tumor-cell intrinsic type-I interferon signaling, upregulation of MHC-I expression, and increased CD8+ T-cell infiltration. Importantly, spontaneous immune clearance observed in Setdb1-/- tumors results in subsequent protection from other ERV-expressing tumor lines, supporting the functional anti-tumor role of ERV-specific CD8+ T-cells found in the Setdb1-/- microenvironment. Blocking the type-I interferon receptor in mice grafted with Setdb1-/- tumors decreases immunogenicity by decreasing MHC-I expression, leading to decreased T-cell infiltration and increased melanoma growth, comparable to Setdb1wt tumors. Together, these results provide key in vivo evidence of a critical role for Setdb1 and type-I interferons in generating an inflamed tumor microenvironment, and potentiating tumor-cell intrinsic immunogenicity in melanoma. This study further emphasizes regulators of ERV expression and type-I interferon expression as potential therapeutic targets for augmenting anti-cancer immune responses.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yameng Hao, Aspasia Gkasti, Amy J Managh, Julien Dagher, Alexandros Sifis, Luca Tiron, Louis-Emmanuel Chriqui, Damien N Marie, Olga De Souza Silva, Michel Christodoulou, Solange Peters, Johanna A Joyce, Thorsten Krueger, Michel Gonzalez, Etienne Abdelnour-Berchtold, Christine Sempoux, Daniel Clerc, Hugo Teixeira-Farinha, Martin Hübner, Etienne Meylan, Paul J Dyson, Sabrina Cavin, Jean Y Perentes
{"title":"Hyperthermic intrathoracic chemotherapy modulates the immune microenvironment of pleural mesothelioma and improves the impact of dual immune checkpoint inhibition.","authors":"Yameng Hao, Aspasia Gkasti, Amy J Managh, Julien Dagher, Alexandros Sifis, Luca Tiron, Louis-Emmanuel Chriqui, Damien N Marie, Olga De Souza Silva, Michel Christodoulou, Solange Peters, Johanna A Joyce, Thorsten Krueger, Michel Gonzalez, Etienne Abdelnour-Berchtold, Christine Sempoux, Daniel Clerc, Hugo Teixeira-Farinha, Martin Hübner, Etienne Meylan, Paul J Dyson, Sabrina Cavin, Jean Y Perentes","doi":"10.1158/2326-6066.CIR-24-0245","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0245","url":null,"abstract":"<p><p>Pleural mesothelioma (PM) is a fatal disease with limited treatment options. Recently, PM management has improved with the development of immune checkpoint inhibitors (ICIs). In first-line therapy, dual PD-1 and CTLA-4 blockade enhances tumor control and patient survival compared with chemotherapy. Unfortunately, only a fraction of patients is responsive to immunotherapy, and approaches to reshape the tumor immune microenvironment and make ICIs more effective are urgently required. Here, we evaluated the effect of Hyperthermic IntraThOracic Chemotherapy (HITOC), a treatment that combines fever-range hyperthermia with local intrapleural cisplatin chemotherapy, on the tumor immune microenvironment and response to ICIs. To do this, we developed a murine PM model of HITOC. We found that HITOC significantly improved tumor control and animal survival through a mechanism involving the development of a cytotoxic immune response. Additionally, HITOC enhanced immune checkpoint expression by T lymphocytes and synergized with dual PD-1 and CTLA-4 inhibition, leading to further improvement in animal survival. Finally, the analysis of peritoneal mesothelioma patient samples treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) revealed a similar immunomodulation. In conclusion, HITOC remodels the tumor immune microenvironment of PM by promoting T-cell infiltration into the tumor and could be considered in combination with ICIs in the context of a clinical trial.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD49a targeting enhances NK cell function and antitumor immunity.","authors":"Yu Zhang, Yangyang Li, Zhengfeng Zhang, Xiaodong Zheng, Hui Peng, Zhigang Tian, Rui Sun, Haoyu Sun","doi":"10.1158/2326-6066.CIR-24-0124","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-24-0124","url":null,"abstract":"<p><p>Approximately 70% of patients receiving immune checkpoint blockade therapies develop treatment resistance. Thus, there is a need for the identification of additional immunotherapeutic targets. CD49a is a membrane protein expressed on NK cells and T cells. In this study, we found that CD49a was highly expressed on the surface of tumor-infiltrating NK cells in various mouse tumor models, and that CD49a+ tumor-infiltrating NK cells were more exhausted than CD49a- tumor-infiltrating NK cells. Furthermore, CD49a or NK-specific CD49a deficiency slowed tumor growth and prolonged survival in several mouse tumor models, primarily through the essential role played by NK cells in antitumor activities. Blockade of CD49a using a monoclonal antibody suppressed tumor development in mice and combination treatment with anti-PD-L1 further enhanced antitumor efficacy. Our research reveals CD49a on NK cells as an immunotherapeutic target, and highlights the potential clinical applications of CD49a-targeted therapies.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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