美国哈佛医学院Debattama R. Sen团队发现，老年的肿瘤微环境限制T细胞对癌症的控制。这一研究成果于2024年5月14日在线发表在国际学术期刊《自然—免疫学》上。

附：英文原文

Title: The aged tumor microenvironment limits T cell control of cancer

Author: Chen, Alex C. Y., Jaiswal, Sneha, Martinez, Daniela, Yerinde, Cansu, Ji, Keely, Miranda, Velita, Fung, Megan E., Weiss, Sarah A., Zschummel, Maria, Taguchi, Kazuhiro, Garris, Christopher S., Mempel, Thorsten R., Hacohen, Nir, Sen, Debattama R.

Issue&Volume: 2024-05-14

Abstract: The etiology and effect of age-related immune dysfunction in cancer is not completely understood. Here we show that limited priming of CD8+ T cells in the aged tumor microenvironment (TME) outweighs cell-intrinsic defects in limiting tumor control. Increased tumor growth in aging is associated with reduced CD8+ T cell infiltration and function. Transfer of T cells from young mice does not restore tumor control in aged mice owing to rapid induction of T cell dysfunction. Cell-extrinsic signals in the aged TME drive a tumor-infiltrating age-associated dysfunctional (TTAD) cell state that is functionally, transcriptionally and epigenetically distinct from canonical T cell exhaustion. Altered natural killer cell–dendritic cell–CD8+ T cell cross-talk in aged tumors impairs T cell priming by conventional type 1 dendritic cells and promotes TTAD cell formation. Aged mice are thereby unable to benefit from therapeutic tumor vaccination. Critically, myeloid-targeted therapy to reinvigorate conventional type 1 dendritic cells can improve tumor control and restore CD8+ T cell immunity in aging.

DOI: 10.1038/s41590-024-01828-7

Source: https://www.nature.com/articles/s41590-024-01828-7