细胞毒性T细胞
癌症研究
CD8型
肿瘤细胞
化学
细胞毒性
生物
细胞生物学
分子生物学
免疫学
免疫系统
体外
生物化学
作者
Zeliang Yang,Liang Liu,Zhenyu Zhu,Zixi Hu,Bowen Liu,Junsong Gong,Yuan Jin,Jian Luo,Yichen Deng,Yan Jin,Guangxi Wang,Yuxin Yin
标识
DOI:10.1002/advs.202304501
摘要
Abstract CD8 + T cells are critical for host antitumor responses, whereas persistent antigenic stimulation and excessive inflammatory signals lead to T cell dysfunction or exhaustion. Increasing early memory T cells can improve T cell persistence and empower T cell‐mediated tumor eradication, especially for adoptive cancer immunotherapy. Here, it is reported that tumor‐associated monocytes (TAMos) are highly correlated with the accumulation of CD8 + memory T cells in human cancers. Further analysis identifies that TAMos selectively reprogram CD8 + T cells into T central memory‐like (T CM ‐like) cells with enhanced recall responses. L‐NMMA, a pan nitric oxide synthase inhibitor, can mitigate TAMo‐mediated inhibition of T cell proliferation without affecting T CM ‐like cell generation. Moreover, the modified T cells by TAMo exposure and L‐NMMA treatment exhibit long‐term persistence and elicit superior antitumor effects in vivo. Mechanistically, the transmembrane protein CD300LG is involved in TAMo‐mediated T CM ‐like cell polarization in a cell‐cell contact‐dependent manner. Thus, the terminally differentiated TAMo subset (CD300LG high ACE low ) mainly contributes to T CM ‐like cell development. Taken together, these findings establish the significance of TAMos in boosting T‐cell antitumor immunity.
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