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

Abstract

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.