| First Author | Wu B | Year | 2023 |
| Journal | J Immunother Cancer | Volume | 11 |
| Issue | 2 | PubMed ID | 36731891 |
| Mgi Jnum | J:354057 | Mgi Id | MGI:7719107 |
| Doi | 10.1136/jitc-2022-005852 | Citation | Wu B, et al. (2023) BRCA1 deficiency in mature CD8(+) T lymphocytes impairs antitumor immunity. J Immunother Cancer 11(2) |
| abstractText | 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. |
