BRCA gene mutations do not shape the extent and organization of tumor infiltrating lymphocytes in triple negative breast cancer

Cancer Letters
Cinzia SolinasKaren Willard-Gallo

Abstract

This study investigated the prevalence of TIL subpopulations, TLS, PD-1 and PD-L1 in tumors from TNBC patients harboring wild-type or mutated BRCA1 or BRCA2 germline genes. This TNBC cohort included 85% TIL-positive (≥10%) tumors with 21% classified as TILhi (≥50%). Interestingly, the BRCAmut group had a significantly higher incidence of TILpos tumors compared to the BRCAwt group (P = 0.037). T cells were dominant in the infiltrate but no statistically significant differences were detected between BRCAwt and BRCAmut for CD3+, CD4+ and CD8+ T cells or CD20+ B cells. TLS were detected in 74% of tumors but again no significant differences between the BRCA groups. PD-1 expression was observed in 33% and PD-L1 in 53% (any cell, cut-off ≥1%) tumors for the entire TNBC cohort. PD-1 expression correlated with PD-L1 and both with TIL and TLS but was not associated with BRCA mutational status. Our analyses reveal that BRCAwt and BRCAmut TNBC are similar except for a significant increase of TILpos tumors in the BRCAmut group. While BRCA gene mutations may not directly drive immune infiltration, the greater number of TILpos tumors could signal greater immunogenicity in this group.

Citations

Dec 14, 2019·Current Opinion in Obstetrics & Gynecology·Marcus Schmidt
Jan 21, 2020·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Leonora de BooMarleen Kok
Jan 25, 2020·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Carmen Criscitiello, Giuseppe Curigliano
Jul 3, 2021·International Journal of Molecular Sciences·Susan MorandJohn Nemunaitis
Jul 20, 2021·Frontiers in Immunology·Charlotte DomblidesMarie-Caroline Dieu-Nosjean
Aug 20, 2021·The Journal of Clinical Investigation·Grégory NoëlKaren Willard-Gallo
Jan 7, 2022·Science·Ton N Schumacher, Daniela S Thommen

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