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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Lingyun Xu and Chen Li*

DOI: 10.2174/1871520621666210618100857

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

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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.

Methods: Single-cell sequencing data of TNBC patients from the GSE118389 dataset were analyzed to examine the immune environment and intratumoral heterogeneity of TNBC patients.

Results: 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.

Keywords: Single-cell transcriptome, immune ecosystem, triple-negative breast cancer, activated macrophages, exhausted CD8+ T cells, immunosuppressive checkpoint.

Graphical Abstract

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