RESUMO
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.
RESUMO
Immuno-oncology treatments have revolutionized the therapeutic options for many types of cancer. The rapid clinical translation of the research results from the past decades has enabled the spread of immune checkpoint inhibitor therapy. In addition to cytokine treatments that modulate anti-tumor immunity, major advances have also been made in adoptive cell therapy, especially regarding the expansion and readministration of tumor-infiltrating lymphocytes. The study of genetically modified T cells is more advanced in hematological malignancies while the applicability in solid tumors is widely investigated. Neoantigens determine antitumor immunity, and neoantigen-based vaccines might contribute to therapy optimization. In this review, we present the diversity of immuno-oncology treatments both that are currently in use and those that are investigated in the research field.
