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BRCA1 deficiency in mature CD8 T lymphocytes impairs antitumor immunity. | LitMetric

AI Article Synopsis

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896206PMC
http://dx.doi.org/10.1136/jitc-2022-005852DOI Listing

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