BRCA1 deficiency in mature CD8 T lymphocytes impairs antitumor immunity

Authors

• Bogang Wu, Department of Biochemistry & Molecular Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, District of Columbia, USA.
• Leilei Qi, Department of Anatomy & Cell Biology, School of Medicine & Health Sciences, The George Washington University, Washington, District of Columbia, USA.
• Huai-Chin Chiang, Department of Biochemistry & Molecular Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, District of Columbia, USA.
• Haihui Pan, Department of Biochemistry & Molecular Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, District of Columbia, USA.
• Xiaowen Zhang, Department of Biochemistry & Molecular Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, District of Columbia, USA.
• Alexandra Greenbaum, Ruth Paul Cancer Genetics and Prevention Program, Medical Faculty Associates, The George Washington University, Washington, District of Columbia, USA.
• Elizabeth Stark, Ruth Paul Cancer Genetics and Prevention Program, Medical Faculty Associates, The George Washington University, Washington, District of Columbia, USA.
• Li-Ju Wang, Department of Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
• Yidong Chen, Department of Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
• Bassem R. Haddad, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA.
• Dionyssia Clagett, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA.
• Claudine Isaacs, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USA.
• Richard Elledge, San Antonio State Hospital, San Antonio, Texas, USA.
• Anelia Horvath, Department of Biochemistry & Molecular Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, District of Columbia, USA.
• Yanfen Hu, Department of Anatomy & Cell Biology, School of Medicine & Health Sciences, The George Washington University, Washington, District of Columbia, USA.
• Rong Li, Department of Biochemistry & Molecular Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, District of Columbia, USA rli69@gwu.edu.

Document Type

Journal Article

Publication Date

2-1-2023

Journal

Journal for immunotherapy of cancer

Volume

11

Issue

2

DOI

10.1136/jitc-2022-005852

Keywords

Adaptive Immunity; Breast Neoplasms; CD8-Positive T-Lymphocytes

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.

APA Citation

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.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2469

Department

Biochemistry and Molecular Medicine