Senescent CD8+ T cells acquire NK cell‐like innate functions to promote antitumor immunity

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Abstract
It has been suggested that aging of the immune system (immunosenescence) results in a decline in the acquired immune response, which is associated with an increase in age‐related tumorigenesis. T‐cell senescence plays a critical role in immunosenescence and is involved in the age‐related decline of the immune function, which increases susceptibility to certain cancers. However, it has been shown that CD8+ T cells with the senescent T‐cell phenotype acquire an natural killer (NK) cell‐like function and are involved in tumor elimination. Therefore, the role of senescent CD8+ T cells in tumor immunity remains to be elucidated. In this study, we investigated the role of senescent CD8+ T cells in tumor immunity. In a murine model of transferred with B16 melanoma, lung metastasis was significantly suppressed in aged mice (age ≥30 weeks) in comparison to young mice (age 6–10 weeks). We evaluated the cytotoxic activity of CD8+ T cells in vitro and found that CD8+ T cells from aged mice activated in vitro exhibited increased cytotoxic activity in comparison to those from young mice. We used Menin‐deficient effector T cells as a model for senescent CD8+ T cells and found that cytotoxic activity and the expression of NK receptors were upregulated in Menin‐deficient senescent CD8+ T cells. Furthermore, Menin‐deficient CD8+ T cells can eliminate tumor cells in an antigen‐independent manner. These results suggest that senescent effector CD8+ T cells may contribute to tumor immunity in the elderly by acquiring NK‐like innate immune functions, such as antigen‐independent cytotoxic activity.
Funding Information
  • Japan Society for the Promotion of Science (20H03504, 22K07121, 22K15609)

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