BRCA1 deficiency in mature CD8+ T lymphocytes impairs antitumor immunity. Issue 2 (2nd February 2023)

• Record Type: Journal Article
• Authors: 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; Li, Rong
• Is Part Of: Journal for immunotherapy of cancer. Volume 11:Issue 2(2023)
• Publication Date: 2023-02-02
• Subjects: Breast Neoplasms -- CD8-Positive T-Lymphocytes -- Adaptive Immunity; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2022-005852
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Women with BRCA1 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 BRCA1 deficiency in non-breast somatic cells also contribute to tumorigenesis. Here, we report that mouse Brca1 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 Brca1 KO on antitumor adaptive immunity. T cell-specific Brca1 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 BRCA1 mutation-carrying women display lower abundance of circulating CD8 + lymphocytes than the age-matched control group. Thus, our findings support the notion that BRCA1 deficiency in adaptive immunity could contribute to BRCA1 -related tumorigenesis. We also suggest that prophylactic boosting of adaptive immunity may reduce cancer incidence among at-risk women.