Tumor‐Associated Monocytes Reprogram CD8<sup>+</sup> T Cells into Central Memory‐Like Cells with Potent Antitumor Effects
Zeliang Yang, Liang Liu, Zhenyu Zhu, Zixi Hu, Bowen Liu, Jingjing Gong, Yuan Jin, Juan Luo, Yichen Deng, Yan Jin, Guangxi Wang, Yuxin Yin
Abstract
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.