文献类型： 外文期刊

作者： Cao, Limin ¹ ; Wang, Li ¹ ; Li, Zhihong ³ ; Wei, Xia ⁴ ; Ding, Jinqiu ¹ ; Zhou, Chun ⁵ ; Chen, Xia ⁸ ; Huang, Zhicheng ¹ ; Shao, Zhugui ¹ ; Shen, Junchen ¹ ; Lou, Hongfei ⁵ ; Zhao, Keqing ⁵ ; Huang, Yuwei ¹¹ ; Yang, Yuanqin ⁴ ; Liu, Han ⁷ ; Sun, Yumeng ¹ ; Niu, Junling ¹ ; Jiang, Shan ¹ ; Lu, Rong ¹² ; Tang, Longhai ¹² ; Zhang, Xiaoming ¹ ; Zhang, Haibing ⁷ ; Xiao, Yichuan ⁷ ; Chen, Jianfeng ¹³ ; Ma, Shixin ¹⁴ ; Gao, Chengjiang ⁹ ; Meng, Guangxun ¹ ; Liu, Li ³ ; Qiu, Zhaozhu ¹⁵ ; Wang, Haopeng ¹¹ ; Deng, Liufu ¹⁸ ; Ye, Youqiong ⁴ ; Jia, Xin-Ming ² ; Li, Huabin ⁵ ; Xiao, Hui ¹ ;

作者机构： 1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Immun & Infect, State Key Lab Immune Response & Immunotherapy, Shanghai 200031, Peoples R China

2.Tongji Univ, Shanghai Pulm Hosp, Clin Translat Res Ctr, Sch Med, Shanghai 200092, Peoples R China

3.China State Inst Pharmaceut Ind, Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, Shanghai 200437, Peoples R China

4.Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Dept Immunol & Microbiol, Sch Med, Shanghai 200025, Peoples R China

5.Fudan Univ, Affiliated Eye Ear Nose & Throat Hosp, Ctr Allerg & Inflammatory Dis, Shanghai 200031, Peoples R China

6.Fudan Univ, Affiliated Eye Ear Nose & Throat Hosp, Dept Otolaryngol Head & Neck Surg, Shanghai 200031, Peoples R China

7.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Nutr Metab & Food Safety, Shanghai 200031, Peoples R China

8.Lanzhou Univ, Chinese Acad Agr Sci, Lanzhou Vet Res Inst, Coll Vet Med,State Key Lab Anim Dis Control & Pre, Lanzhou 730000, Peoples R China

9.Shandong Univ, Sch Biomed Sci, Key Lab Infect & Immun Shandong Prov, Jinan 250012, Shandong, Peoples R China

10.Shandong Univ, Sch Biomed Sci, Dept Immunol, Jinan 250012, Peoples R China

11.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

12.Suzhou Blood Ctr, Suzhou 215000, Jiangsu, Peoples R China

13.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol, Shanghai 200031, Peoples R China

14.Shenzhen Med Acad Res & Translat, Shenzhen 518107, Guangdong, Peoples R China

15.Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

16.Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

17.Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA

18.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China

期刊名称：SCIENCE IMMUNOLOGY （ 影响因子：16.3； 五年影响因子：17.7 ）

ISSN： 2470-9468

年卷期： 2025 年 10 卷 108 期

页码：

收录情况： SCI

摘要： The volume-regulated anion channels (VRACs) transport osmolytes, neurotransmitters, and cyclic GMP-AMP (cGAMP) across the cell membrane to regulate cell volume and host defense. We report that the leucine-rich repeat-containing 8A/C (LRRC8A/C) VRAC plays a crucial role in immune responses to radiotherapy and chemotherapy for cancer. VRACs transfer cGAMP from irradiated cancer cells to infiltrating CD4 and CD8 T cells, thus enhancing their effector functions. TCR signaling acts as a physiological signal to open the VRAC pore through phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and reactive oxygen species (ROS). This allows the rapid uptake of cGAMP and STING activation in mouse and human T cells and induction of interferon-alpha/beta, which up-regulate granzymes and IFN-gamma in CD8 T cells. Inhibition of the extracellular hydroxylases CD39 and ENPP1 maintains extracellular ATP and cGAMP, which promotes VRAC-enhanced CD8 T cell anticancer function. Thus, the transfer of cGAMP to T cells by VRACs may be a strategy that can be targeted in future cancer therapies.