Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Sci Rep. 2021 Feb 25;11(1):4691. doi: 10.1038/s41598-021-83913-7.
Studies have shown that the presence of tumor infiltrating lymphocytes (TILs) in Triple Negative Breast Cancer (TNBC) is associated with better prognosis. However, the molecular mechanisms underlying these immune cell differences are not well delineated. In this study, analysis of hematoxylin and eosin images from The Cancer Genome Atlas (TCGA) breast cancer cohort failed to show a prognostic benefit of TILs in TNBC, whereas CIBERSORT analysis, which quantifies the proportion of each immune cell type, demonstrated improved overall survival in TCGA TNBC samples with increased CD8 T cells or CD8 plus CD4 memory activated T cells and in Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) TNBC samples with increased gamma delta T cells. Twenty-five genes showed mutational frequency differences between the TCGA high and low T cell groups, and many play important roles in inflammation or immune evasion (ATG2B, HIST1H2BC, PKD1, PIKFYVE, TLR3, NOTCH3, GOLGB1, CREBBP). Identification of these mutations suggests novel mechanisms by which the cancer cells attract immune cells and by which they evade or dampen the immune system during the cancer immunoediting process. This study suggests that integration of mutations with CIBERSORT analysis could provide better prediction of outcomes and novel therapeutic targets in TNBC cases.
研究表明，三阴性乳腺癌（TNBC）中肿瘤浸润淋巴细胞（TILs）的存在与更好的预后相关。然而，这些免疫细胞差异的分子机制尚不清楚。本研究对癌症基因组图谱（TCGA）乳腺癌队列的苏木精和伊红图像进行分析，未能显示 TILs 在 TNBC 中的预后获益，而 CIBERSORT 分析可定量每种免疫细胞类型的比例，表明在 TCGA TNBC 样本中，CD8 T 细胞或 CD8 加 CD4 记忆激活 T 细胞增加，以及在乳腺癌国际联合会（METABRIC）的 TNBC 样本中，γδ T 细胞增加，总生存率得到改善。在 TCGA 高 T 细胞组和低 T 细胞组之间，有 25 个基因显示出突变频率的差异，其中许多基因在炎症或免疫逃逸中发挥重要作用（ATG2B、HIST1H2BC、PKD1、PIKFYVE、TLR3、NOTCH3、GOLGB1、CREBBP）。这些突变的鉴定提示了癌细胞吸引免疫细胞的新机制，以及它们在癌症免疫编辑过程中逃避或抑制免疫系统的新机制。本研究表明，将突变与 CIBERSORT 分析相结合，可能为 TNBC 病例提供更好的预后预测和新的治疗靶点。
