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

Abstract

Background: 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. Objective: 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. Method: Single-cell sequencing data of TNBC patients from the GSE118389 dataset were analyzed to examine the immune environment and intratumoral heterogeneity of TNBC patients. Result: 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. Conclusion: Overall, these findings demonstrate inter-tissue heterogeneity of TNBC, and provides novel therapeutic targets for the treatment of TNBC.