Kulturális és Innovációs Minisztérium Új Nemzeti Kiválósági Ösztöndíja(ÚNKP-22-5-SE-25)
Funder: Ministry of Culture and Innovation
(ÚNKP-23-5-SE-16)
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.
