肿瘤相关单核细胞将 CD8(+) T 细胞重编程为具有强效抗肿瘤作用的中央记忆样细胞

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.