BRCA1 deficiency in mature CD8 T lymphocytes impairs antitumor immunity
Journal for immunotherapy of cancer
Adaptive Immunity; Breast Neoplasms; CD8-Positive T-Lymphocytes
Women with germline mutations have approximately an 80% lifetime chance of developing breast cancer. While the tumor suppressor function of BRCA1 in breast epithelium has been studied extensively, it is not clear whether deficiency in non-breast somatic cells also contribute to tumorigenesis. Here, we report that mouse knockout (KO) in mature T lymphocytes compromises host antitumor immune response to transplanted syngeneic mouse mammary tumors. T cell adoptive transfer further corroborates CD8 T cell-intrinsic impact of KO on antitumor adaptive immunity. T cell-specific KO mice exhibit fewer total CD8, more exhausted, reduced cytotoxic, and reduced memory tumor-infiltrating T cell populations. Consistent with the preclinical data, cancer-free mutation-carrying women display lower abundance of circulating CD8 lymphocytes than the age-matched control group. Thus, our findings support the notion that deficiency in adaptive immunity could contribute to -related tumorigenesis. We also suggest that prophylactic boosting of adaptive immunity may reduce cancer incidence among at-risk women.
Wu, Bogang; Qi, Leilei; Chiang, Huai-Chin; Pan, Haihui; Zhang, Xiaowen; Greenbaum, Alexandra; Stark, Elizabeth; Wang, Li-Ju; Chen, Yidong; Haddad, Bassem R.; Clagett, Dionyssia; Isaacs, Claudine; Elledge, Richard; Horvath, Anelia; Hu, Yanfen; and Li, Rong, "BRCA1 deficiency in mature CD8 T lymphocytes impairs antitumor immunity" (2023). GW Authored Works. Paper 2469.
Biochemistry and Molecular Medicine