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Suppression of Tumor or Host Intrinsic CMTM6 Drives Antitumor Cytotoxicity in a PD-L1-Independent Manner

文献类型：期刊论文

作者Long, Yiru4,5; Chen, Runqiu3,4,5; Yu, Xiaolu4,5; Tong, Yongliang4,5; Peng, Xionghua5; Li, Fanglin4,5; Hu, Chao3,4,5; Sun, Jianhua4,5; Gong, Likun1,2,4,5
刊名CANCER IMMUNOLOGY RESEARCH
出版日期2023-02-01
卷号11期号:2页码:241-260
DOI10.1158/2326-6066.CIR-22-0439
文献子类Article
英文摘要CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) is known to be a regulator of membranal programmed death ligand 1 (PD-L1) stability and a factor associated with malignancy progression, but the effects and mechanisms of CMTM6 on tumor growth, as well as its potential as a target for therapy, are still largely unknown. Here, we show that CMTM6 expression increased with tumor progression in both patients and mice. Ablation of CMTM6 significantly reduced human and murine tumor growth in a manner dependent on T-cell immunity. Tumor CMTM6 suppression broke resistance to immune-checkpoint inhibitors and remodeled the tumor immune microenvironment, as specific antitumor cytotoxicity was enhanced and contributed primarily to tumor inhibition. Without the PD-1/PD-L1 axis, CMTM6 suppression still significantly dampened tumor growth dependent on cytotoxic cells. Furthermore, we identified that CMTM6 was widely expressed on immune cells. T-cell CMTM6 levels increased with sustained immune activation and intratumoral immune exhaustion and affected T cell-intrinsic PD-L1 levels. Host CMTM6 knockout significantly restrained tumor growth in a manner dependent on CD8(+) T cells and not entirely dependent on PD-L1. Thus, we developed and evaluated the antitumor efficacy of CMTM6-targeting adeno-associated virus (AAV), which effectively mobilized antitumor immunity and could be combined with various antitumor drugs. Our findings reveal that both tumor and host CMTM6 are involved in antitumor immunity with or without the PD-1/PD-L1 axis and that gene therapy targeting CMTM6 is a promising strategy for cancer immunotherapy.
WOS关键词EXPRESSION ; PD-L1 ; IDENTIFICATION ; PATHWAY ; CANCER ; MARVEL
WOS研究方向Oncology ; Immunology
语种英语
WOS记录号WOS:000927475000001
出版者AMER ASSOC CANCER RESEARCH
源URL[http://119.78.100.183/handle/2S10ELR8/309713]  
专题新药研究国家重点实验室
通讯作者Gong, Likun
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Hai-Ke Rd, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China;
3.Shenyang Pharmaceut Univ, Wuya Coll Innovat, Dept Pharmaceut, Shenyang, Peoples R China;
4.Univ Chinese Acad Sci, Beijing, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Long, Yiru,Chen, Runqiu,Yu, Xiaolu,et al. Suppression of Tumor or Host Intrinsic CMTM6 Drives Antitumor Cytotoxicity in a PD-L1-Independent Manner[J]. CANCER IMMUNOLOGY RESEARCH,2023,11(2):241-260.
APA Long, Yiru.,Chen, Runqiu.,Yu, Xiaolu.,Tong, Yongliang.,Peng, Xionghua.,...&Gong, Likun.(2023).Suppression of Tumor or Host Intrinsic CMTM6 Drives Antitumor Cytotoxicity in a PD-L1-Independent Manner.CANCER IMMUNOLOGY RESEARCH,11(2),241-260.
MLA Long, Yiru,et al."Suppression of Tumor or Host Intrinsic CMTM6 Drives Antitumor Cytotoxicity in a PD-L1-Independent Manner".CANCER IMMUNOLOGY RESEARCH 11.2(2023):241-260.

入库方式： OAI收割

来源：上海药物研究所

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