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Immunosuppressive microenvironment restrains chemotherapy efficacy in liver metastases of triple-negative breast cancer

ABSTRACT: This study investigates the role of the immune microenvironment in the efficacy of chemotherapy for triple-negative breast cancer (TNBC) liver metastases compared to primary tumors. Using mouse models, we assessed chemotherapeutic efficacy and characterized intratumoral T lymphocytes and macrophages via RNA sequencing, immunohistochemistry, and flow cytometry. We found that liver metastases had a less effective response to chemotherapy compared to subcutaneous tumors, linked to reduced CD8+ T cell infiltration and macrophage activation. Chemotherapy induced an immunosuppressive shift, with neutrophil extracellular traps (NETs) accumulating in liver metastases and macrophages and T cells showing impaired functionality in the primary tumors. Combining macrophage activators or NETs inhibitors with chemotherapy improved outcomes. Our findings highlight the importance of tumor site-specific immune microenvironmental differences in chemotherapy responses and suggest that targeted therapies could enhance chemotherapy efficacy.

ORGANISM(S): Mus musculus

PROVIDER: GSE276098 | GEO | 2025/06/25

REPOSITORIES: GEO

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Neutrophil Extracellular Traps induced by chemotherapy inhibit tumor growth in vivo

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Immunosuppressive microenvironment restrains chemotherapy efficacy in liver metastases of triple-negative breast cancer

Project description:Immunosuppressive microenvironment restrains chemotherapy efficacy in liver metastases of triple-negative breast cancer

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