Single-Cell Transcriptome Analysis Reveals the M2 Macrophages and Exhausted T Cells and Intratumoral Heterogeneity in Triple-Negative Breast Cancer.

Abstract

Triple-Negative Breast Cancer (TNBC) is a highly heterogeneous and invasive malignancy that is characterized by high recurrence and mortality rates as well as extremely poor prognosis. The objective of this study is to analyze T cells and Macrophages in the tumor microenvironment with the aim of identifying targets with therapeutic potential. Single-cell sequencing data of TNBC patients from the GSE118389 dataset were analyzed to examine the immune environment and intratumoral heterogeneity of TNBC patients. Polarized alternatively activated macrophages (M2) and exhausted CD8+ T cells were identified in TNBC patients. Immunosuppressive checkpoint analysis revealed that levels of lymphocyte-activation gene 3 (LAG3) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) of exhausted T cells were significantly higher than levels of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4). This indicates that these markers are potential immunotherapy targets. Furthermore, analysis of significantly altered immune cell markers showed that several markers were associated with the prognosis of TNBC. Overall, these findings demonstrate inter-tissue heterogeneity of TNBC, and provides novel therapeutic targets for the treatment of TNBC.