Peripheral immunophenotyping reveals lymphocyte stimulation in healthy women living with hereditary breast and ovarian cancer syndrome

Balog, József Ágoston and Horti-Oravecz, Klaudia and Kövesdi, Dorottya and Bozsik, Anikó and Papp, Janos and Butz, Henriett and Patócs, Attila and Szebeni, Gábor János and Grolmusz, Vince Kornél (2024) Peripheral immunophenotyping reveals lymphocyte stimulation in healthy women living with hereditary breast and ovarian cancer syndrome. iScience, 27 (6). No.-109882. ISSN 25890042

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Abstract

Germline pathogenic variants in BRCA1 and BRCA2 (gpath(BRCA1/2)) represent genetic susceptibility for hereditary breast and ovarian cancer syndrome. Tumor-immune interactions are key contributors to breast cancer pathogenesis. Although earlier studies confirmed pro-tumorigenic immunological alterations in breast cancer patients, data are lacking in healthy carriers of gpath(BRCA1/2). Peripheral blood mononuclear cells of 66 women with or without germline predisposition or breast cancer were studied with a mass cytometry panel that identified 4 immune subpopulations of altered frequencies between healthy controls and healthy gpath(BRCA1) carriers, while no difference was observed in healthy gpath(BRCA2) carriers compared to controls. Moreover, 3 (one IgD-CD27+CD95+ B cell subpopulation and two CD45RA-CCR7+CD38+ CD4+ T cell subpopulations) out of these 4 subpopulations were also elevated in triple-negative breast cancer patients compared to controls. Our results reveal an activated peripheral immune phenotype in healthy carriers of gpath(BRCA1) that needs to be further elucidated to be leveraged in risk-reducing strategies.

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