Carcinomas exhibiting epithelial–mesenchymal transition manifest an M2 macrophage-enriched tumor immune microenvironment

作者：Huang‐Chun Lien, Yu-Chia Li, Ruby Yun‐Ju Huang, Ko-Chen Chen, Tom Wei‐Wu Chen, I‐Chun Chen, Li-Ping Hsiao, Ling-Chun Yeh, Yen‐Shen Lu · 发表于：Breast Cancer Research · 年份：2025 · DOI：10.1186/s13058-025-02119-1 · 被引用次数：3 · 研究领域：Immune cells in cancer、Cancer Cells and Metastasis、Metastasis and carcinoma case studies

Abstract Background Epithelial–mesenchymal transition (EMT) is linked to an immunosuppressive tumor microenvironment (TME). However, direct comparisons of the TME in paired tumor regions with and without EMT in primary tumors—essential for elucidating EMT’s impact on the TME—are still lacking. Methods Using Digital Spatial Profiler (DSP) assay and NanoString nCounter Digital Profiling, we analyzed immune-oncology-related markers in the TME of no special type (NST) and paired spindle carcinomatous (SPS) components, the later considered the EMT counterpart of the former, in nine cases of metaplastic breast carcinoma, a type of mammary carcinosarcoma. Results We identified macrophage markers as consistently and significantly enriched immune-oncology-related proteins within the TME profiles of SPS components compared to their paired NST counterparts. Additionally, we observed notable enrichment of macrophage-related signatures, M2 macrophage phenotypes, M2 macrophage-inducing cytokines, and M2 macrophage-related genes, as key distinctions in the TME profiles of SPS components relative to NST counterparts. Immunohistochemistry and multiplex immunofluorescence confirmed the presence of M2 macrophages, predominantly characterized by CD14 + /CD68 + /CD163 + phenotypes, in the SPS components. The in vivo findings were supported by in vitro analysis, which revealed that primary breast cancer cells undergoing spontaneous EMT exhibit enhanced induction of M2 macrophage polarization, with...