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

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 TIL^hi (≥50%). Interestingly, the BRCA^mut group had a significantly higher incidence of TIL^pos tumors compared to the BRCA^wt group (P = 0.037). T cells were dominant in the infiltrate but no statistically significant differences were detected between BRCA^wt and BRCA^mut 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 BRCA^wt and BRCA^mut TNBC are similar except for a significant increase of TIL^pos tumors in the BRCA^mut group. While BRCA gene mutations may not directly drive immune infiltration, the greater number of TIL^pos tumors could signal greater immunogenicity in this group.

Keywords: BRCA gene mutations; PD-1 and PD-L1; Tertiary lymphoid structures; Triple negative breast cancer; Tumor infiltrating lymphocytes.