Peripheral immunophenotyping reveals lymphocyte stimulation in healthy women living with hereditary breast and ovarian cancer syndrome
József Ágoston Balog,
Klaudia Horti-Oravecz,
Dorottya Kövesdi,
Anikó Bozsik,
Janos Papp,
Henriett Butz,
Attila Patócs,
Gábor János Szebeni,
Vince Kornél Grolmusz
Affiliations
József Ágoston Balog
Institute of Genetics, Laboratory of Functional Genomics, HUN-REN Biological Research Center, 6726 Szeged, Hungary; Core Facility, HUN-REN Biological Research Center, 6726 Szeged, Hungary
Klaudia Horti-Oravecz
Department of Molecular Genetics and the National Tumorbiology Laboratory, National Institute of Oncology, Comprehensive Cancer Center, 1122 Budapest, Hungary; Semmelweis University, Doctoral School, 1085 Budapest, Hungary
Dorottya Kövesdi
Department of Immunology, Eötvös Loránd University, 1117 Budapest, Hungary
Anikó Bozsik
Department of Molecular Genetics and the National Tumorbiology Laboratory, National Institute of Oncology, Comprehensive Cancer Center, 1122 Budapest, Hungary; HUN-REN-SE Hereditary Cancers Research Group, Hungarian Research Network – Semmelweis University, 1122 Budapest, Hungary
Janos Papp
Department of Molecular Genetics and the National Tumorbiology Laboratory, National Institute of Oncology, Comprehensive Cancer Center, 1122 Budapest, Hungary; HUN-REN-SE Hereditary Cancers Research Group, Hungarian Research Network – Semmelweis University, 1122 Budapest, Hungary
Henriett Butz
Department of Molecular Genetics and the National Tumorbiology Laboratory, National Institute of Oncology, Comprehensive Cancer Center, 1122 Budapest, Hungary; HUN-REN-SE Hereditary Cancers Research Group, Hungarian Research Network – Semmelweis University, 1122 Budapest, Hungary; Department of Oncology Biobank, National Institute of Oncology, Comprehensive Cancer Center, 1122 Budapest, Hungary; Department of Laboratory Medicine, Semmelweis University, 1089 Budapest, Hungary
Attila Patócs
Department of Molecular Genetics and the National Tumorbiology Laboratory, National Institute of Oncology, Comprehensive Cancer Center, 1122 Budapest, Hungary; HUN-REN-SE Hereditary Cancers Research Group, Hungarian Research Network – Semmelweis University, 1122 Budapest, Hungary; Department of Laboratory Medicine, Semmelweis University, 1089 Budapest, Hungary
Gábor János Szebeni
Institute of Genetics, Laboratory of Functional Genomics, HUN-REN Biological Research Center, 6726 Szeged, Hungary; Core Facility, HUN-REN Biological Research Center, 6726 Szeged, Hungary; Department of Internal Medicine, Hematology Centre, Faculty of Medicine University of Szeged, 6725 Szeged, Hungary; Corresponding author
Vince Kornél Grolmusz
Department of Molecular Genetics and the National Tumorbiology Laboratory, National Institute of Oncology, Comprehensive Cancer Center, 1122 Budapest, Hungary; HUN-REN-SE Hereditary Cancers Research Group, Hungarian Research Network – Semmelweis University, 1122 Budapest, Hungary; Department of Laboratory Medicine, Semmelweis University, 1089 Budapest, Hungary; Corresponding author
Summary: 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.
