Cancer immunology research最新文献_第7页

CD49a Targeting Enhances NK Cell Function and Antitumor Immunity. CD49a 靶向可增强 NK 细胞功能和抗肿瘤免疫力。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2025-01-09 DOI: 10.1158/2326-6066.CIR-24-0124

Yu Zhang, Yangyang Li, Zhengfeng Zhang, Xiaodong Zheng, Hui Peng, Zhigang Tian, Rui Sun, Haoyu Sun

引用次数: 0

Transient EZH2 Suppression by Tazemetostat during In Vitro Expansion Maintains T-Cell Stemness and Improves Adoptive T-Cell Therapy. 在体外扩增过程中用泰泽美司他暂时抑制 EZH2 可保持 T 细胞的干性并改善 T 细胞采纳疗法。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2025-01-09 DOI: 10.1158/2326-6066.CIR-24-0089

Yingqin Hou, Jaroslav Zak, Yujie Shi, Isaraphorn Pratumchai, Brandon Dinner, Wenjian Wang, Ke Qin, Evan W Weber, John R Teijaro, Peng Wu

{"title":"Transient EZH2 Suppression by Tazemetostat during In Vitro Expansion Maintains T-Cell Stemness and Improves Adoptive T-Cell Therapy.","authors":"Yingqin Hou, Jaroslav Zak, Yujie Shi, Isaraphorn Pratumchai, Brandon Dinner, Wenjian Wang, Ke Qin, Evan W Weber, John R Teijaro, Peng Wu","doi":"10.1158/2326-6066.CIR-24-0089","DOIUrl":"10.1158/2326-6066.CIR-24-0089","url":null,"abstract":"The histone methyltransferase enhancer of zeste homolog 2 (EZH2) plays important roles in T-cell differentiation, proliferation, and function. Previous studies have demonstrated that genetic deletion of EZH2 in CD8+ or total T cells impairs their antiviral and antitumor activities, cytokine production, and ability to expand upon rechallenge. Contrary to the detrimental role of deleting T cell-intrinsic EZH2, in this study, we demonstrated that transient inhibition of EZH2 in T cells prior to the phenotypic onset of exhaustion with a clinically approved inhibitor, tazemetostat (Taz), delayed their dysfunctional progression and preserved T-cell stemness and polyfunctionality but had no negative impact on cell proliferation. Taz-induced T-cell epigenetic reprogramming increased the expression of the self-renewal T-cell transcription factor TCF1 by reducing H3K27 methylation at its promoter preferentially in rapidly dividing T cells. In a murine melanoma model, T cells depleted of EZH2 induced poor tumor control, whereas adoptively transferred T cells pretreated with Taz exhibited superior antitumor immunity, especially when used in combination with anti-PD-1 blockade. Collectively, these data highlight the potential of transient epigenetic reprogramming by EZH2 inhibition to enhance adoptive T-cell immunotherapy.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"47-65"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375128","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}

引用次数: 0

Complement Factor H Is an ICOS Ligand Modulating Tregs in the Glioma Microenvironment. 补体因子H是一种ICOS配体，可调节胶质瘤微环境中的集落细胞。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2025-01-09 DOI: 10.1158/2326-6066.CIR-23-1092

Karolina I Smolag, Jakub Olszowka, Rebecca Rosberg, Elinn Johansson, Elisabet Marinko, Karin Leandersson, David J O'Connell, Valeria Governa, Emre Can Tuysuz, Mattias Belting, Alexander Pietras, Myriam Martin, Anna M Blom

{"title":"Complement Factor H Is an ICOS Ligand Modulating Tregs in the Glioma Microenvironment.","authors":"Karolina I Smolag, Jakub Olszowka, Rebecca Rosberg, Elinn Johansson, Elisabet Marinko, Karin Leandersson, David J O'Connell, Valeria Governa, Emre Can Tuysuz, Mattias Belting, Alexander Pietras, Myriam Martin, Anna M Blom","doi":"10.1158/2326-6066.CIR-23-1092","DOIUrl":"10.1158/2326-6066.CIR-23-1092","url":null,"abstract":"The survival rate of patients with glioma has not significantly increased in recent years despite aggressive treatment and advances in immunotherapy. The limited response to treatments is partially attributed to the immunosuppressive tumor microenvironment, in which regulatory T cells (Treg) play a pivotal role in immunologic tolerance. In this study, we investigated the impact of complement factor H (FH) on Tregs within the glioma microenvironment and found that FH is an ICOS ligand. The binding of FH to this immune checkpoint molecule promoted the survival and function of Tregs and induced the secretion of TGFβ and IL10 while suppressing T-cell proliferation. We further demonstrated that cancer cells in human and mouse gliomas directly produce FH. Database investigations revealed that upregulation of FH expression was associated with the presence of Tregs and correlated with worse prognosis for patients with glioma. We confirmed the effect of FH on glioma development in a mouse model, in which FH knockdown was associated with a decrease in the number of ICOS+ Tregs and demonstrated a tendency of prolonged survival (P = 0.064). Because the accumulation of Tregs represents a promising prognostic and therapeutic target, evaluating FH expression should be considered when assessing the effectiveness of and resistance to immunotherapies against glioma.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"122-138"},"PeriodicalIF":8.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388318","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}

引用次数: 0

Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression. 根据 PD-L1 表达对肺癌及其免疫微环境进行空间解析的全转录组学和蛋白质组学分析。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-12-03 DOI: 10.1158/2326-6066.CIR-24-0071

Jaemoon Koh, Dongjoo Lee, Sehui Kim, Seung Geun Song, Bogyeong Han, Hyein Jeong, Young A Kim, Bhumsuk Keam, Se-Hoon Lee, Kwangsoo Kim, Yoon Kyung Jeon, Doo Hyun Chung

{"title":"Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression.","authors":"Jaemoon Koh, Dongjoo Lee, Sehui Kim, Seung Geun Song, Bogyeong Han, Hyein Jeong, Young A Kim, Bhumsuk Keam, Se-Hoon Lee, Kwangsoo Kim, Yoon Kyung Jeon, Doo Hyun Chung","doi":"10.1158/2326-6066.CIR-24-0071","DOIUrl":"10.1158/2326-6066.CIR-24-0071","url":null,"abstract":"The expression of PD-L1 on tumor cells (TC) is used as an immunotherapy biomarker in lung cancer, but heterogeneous intratumoral expression is often observed. To better understand heterogeneity in the lung cancer tumor microenvironment, we performed proteomic and whole-transcriptomic digital spatial profiling analyses of TCs and immune cells (IC) in spatially matched areas based on tumor PD-L1 expression and the status of the immune microenvironment. We validated our findings using IHC, data from The Cancer Genome Atlas, and immunotherapy cohorts. ICs in areas with high PD-L1 expression on TCs showed more features, indicative of immunosuppression and exhaustion, than ICs in areas with low PD-L1 expression on TCs. TCs highly expressing PD-L1 within immune-inflamed areas showed upregulation of proinflammatory processes, whereas TCs highly expressing PD-L1 within immune-deficient areas showed upregulation of various metabolic processes. Using differentially expressed genes of TCs between the immune-inflamed and immune-deficient areas, we identified a prognostic gene signature for lung cancer. In addition, we found that a high ratio of CD8+ cells to M2 macrophages predicted favorable outcomes in patients with PD-L1-expressing lung cancer after immune checkpoint inhibitor therapy. Overall, this study demonstrates that TCs and ICs have distinct spatial features within the lung tumor microenvironment that are related to tumor PD-L1 expression and IC infiltration.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1753-1764"},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131938","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}

引用次数: 0

BTN2A1: A Novel Target to Boost Tumor Killing Capacity of Human γδ T Cells. BTN2A1：提高人类γδ T 细胞杀伤肿瘤能力的新靶点

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-12-03 DOI: 10.1158/2326-6066.CIR-24-0925

Dieter Kabelitz

引用次数: 0

Cannabidiol Enhances Atezolizumab Efficacy by Upregulating PD-L1 Expression via the cGAS-STING Pathway in Triple-Negative Breast Cancer Cells. 大麻二酚通过 cGAS-STING 通路上调三阴性乳腺癌细胞中 PD-L1 的表达，从而增强阿特珠单抗的疗效。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-12-03 DOI: 10.1158/2326-6066.CIR-23-0902

Bu Gyeom Kim, Bo Ram Kim, Dae Yeong Kim, Woo Young Kim, Sanghee Kang, Sun Il Lee, Sang Cheul Oh

{"title":"Cannabidiol Enhances Atezolizumab Efficacy by Upregulating PD-L1 Expression via the cGAS-STING Pathway in Triple-Negative Breast Cancer Cells.","authors":"Bu Gyeom Kim, Bo Ram Kim, Dae Yeong Kim, Woo Young Kim, Sanghee Kang, Sun Il Lee, Sang Cheul Oh","doi":"10.1158/2326-6066.CIR-23-0902","DOIUrl":"10.1158/2326-6066.CIR-23-0902","url":null,"abstract":"The treatment of patients with triple-negative breast cancer (TNBC) relies on cytotoxic therapy. Currently, atezolizumab and chemotherapy can be combined in patients with TNBC. However, this approach is not effective for all patients, with many tumors showing low responsiveness to atezolizumab. As there is a lack of alternative treatment options, new anticancer drugs are urgently needed to enhance atezolizumab activity against TNBC. Recent strategies have focused on regulating the expression of programmed cell death ligand 1 (PD-L1) or enhancing immune response activation by combining anticancer drugs with immune checkpoint inhibitors. Cannabidiol (CBD), a cannabinoid component derived from the cannabis plant, has been reported to have anticancer therapeutic potential because of its capacity to induce apoptotic cell death in tumor cells while avoiding cytotoxicity in normal cells. Previous studies have demonstrated the effects of CBD on apoptosis in various cancer cell types. However, the potential role of CBD as an immune modulator in the regulation of PD-L1 expression and anticancer immune responses remains to be explored. In this study, we found that CBD stimulated PD-L1 expression in TNBC cells and that this occurred downstream of CBD-mediated cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway activation. Taken together, we have demonstrated that the combination of CBD and anti-PD-L1 enhances the anticancer immune responses in in vitro and in vivo experiments. Our findings identified the mechanism of PD-L1 regulation by CBD in TNBC cells and suggested that CBD could be a potential candidate for the development of new combinatorial strategies with immune checkpoint inhibitors in patients with TNBC.","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"1796-1807"},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124909","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}

引用次数: 0

CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis. 经改造可分泌 IFN-κ 的 CAR T 细胞通过 IFNAR/STAT1/ACSL4 轴诱导肿瘤铁变态反应。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-12-03 DOI: 10.1158/2326-6066.CIR-24-0130

Yaoxin Gao, Shasha Liu, Yifan Huang, Hui Wang, Yuyu Zhao, Xuyang Cui, Yajing Peng, Feng Li, Yi Zhang

引用次数: 0

A Sampling of Highlights from the Literature. 从文献中精选的一些亮点。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-12-03 DOI: 10.1158/2326-6066.CIR-12-12-WWR

引用次数: 0

Targeting BTN2A1 Enhances Vγ9Vδ2 T-Cell Effector Functions and Triggers Tumor Cell Pyroptosis. 靶向 BTN2A1 可增强 Vγ9Vδ2 T 细胞效应器功能并引发肿瘤细胞热解。

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-12-03 DOI: 10.1158/2326-6066.CIR-23-0868

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":"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.","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}

引用次数: 0

Correction: CD28 Costimulatory Domain-Targeted Mutations Enhance Chimeric Antigen Receptor T-cell Function. 更正：CD28 Costimulatory Domain-Targeted Mutations Enhance Chimeric Antigen Receptor T-cell Function.

IF 8.1 1区医学

Cancer immunology research Pub Date : 2024-12-03 DOI: 10.1158/2326-6066.CIR-24-1029

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

引用次数: 0