Molecular Immunology Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
IRIBHM, Bioinformatics Laboratory, Université Libre de Bruxelles, Brussels, Belgium.
Cancer Lett. 2019 May 28;450:88-97. doi: 10.1016/j.canlet.2019.02.027. Epub 2019 Feb 22.
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 (≥50%). Interestingly, the BRCA group had a significantly higher incidence of TIL tumors compared to the BRCA group (P = 0.037). T cells were dominant in the infiltrate but no statistically significant differences were detected between BRCA and BRCA 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 and BRCA TNBC are similar except for a significant increase of TIL tumors in the BRCA group. While BRCA gene mutations may not directly drive immune infiltration, the greater number of TIL tumors could signal greater immunogenicity in this group.
本研究调查了在携带野生型或突变型 BRCA1 或 BRCA2 种系基因的 TNBC 患者的肿瘤中 TIL 亚群、TLS、PD-1 和 PD-L1 的流行情况。该 TNBC 队列包括 85% 的 TIL 阳性(≥10%)肿瘤,其中 21% 被归类为 TIL(≥50%)。有趣的是,BRCA 组的 TIL 肿瘤发生率明显高于 BRCA 组(P=0.037)。浸润中的 T 细胞占主导地位,但 BRCA 和 BRCA 之间的 CD3、CD4 和 CD8 T 细胞或 CD20 B 细胞没有统计学上的显著差异。74%的肿瘤中检测到 TLS,但 BRCA 组之间也没有显著差异。整个 TNBC 队列中,33%的肿瘤表达 PD-1,53%(任何细胞,截止值≥1%)的肿瘤表达 PD-L1。PD-1 表达与 PD-L1 以及 TIL 和 TLS 均相关,但与 BRCA 突变状态无关。我们的分析表明,BRCA 和 BRCA TNBC 相似,除了 BRCA 组的 TIL 肿瘤显著增加。虽然 BRCA 基因突变可能不会直接驱动免疫浸润,但在该组中 TIL 肿瘤数量的增加可能表明其具有更高的免疫原性。