Tumor‐Associated Monocytes Reprogram CD8+ T Cells into Central Memory‐Like Cells with Potent Antitumor Effects

• Published in: Advanced science Vol. 11; no. 16; pp. e2304501 - n/a
• Main Authors: Yang, Zeliang, Liu, Liang, Zhu, Zhenyu, Hu, Zixi, Liu, Bowen, Gong, Jingjing, Jin, Yuan, Luo, Juan, Deng, Yichen, Jin, Yan, Wang, Guangxi, Yin, Yuxin
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.04.2024; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Antibodies; Antigens; Cancer therapies; CD300LG; CD8-Positive T-Lymphocytes - immunology; Cell growth; Cell Line, Tumor; Disease Models, Animal; Flow cytometry; Humans; Immunologic Memory - immunology; Immunotherapy, Adoptive - methods; Lung cancer; Lymphocytes; Melanoma; Memory T Cells - immunology; Mice; Mice, Inbred C57BL; Monocytes - immunology; Neoplasms - immunology; Neoplasms - therapy; Neutrophils; Nitric oxide; nitric oxide synthase; Patients; T cell exhaustion; T cell receptors; T central memory‐like cells; Tumors; tumor‐associated monocytes (TAMos); T cell exhaustion; nitric oxide synthase; T central memory‐like cells; CD300LG; tumor‐associated monocytes (TAMos)
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202304501

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 (TCM‐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 TCM‐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 TCM‐like cell polarization in a cell‐cell contact‐dependent manner. Thus, the terminally differentiated TAMo subset (CD300LGhighACElow) mainly contributes to TCM‐like cell development. Taken together, these findings establish the significance of TAMos in boosting T‐cell antitumor immunity. Tumor‐associated monocytes (TAMos) reprogram activated CD8+ T cells to a central memory‐like phenotype with enhanced recall responses, which is mediated by the transmembrane protein CD300LG. CD8+ T cells cocultured with L‐NMMA‐treated TAMos exhibit long‐term persistence and functional fitness in the tumor microenvironment, thereby improving the efficacy of adoptive T cell therapy.