Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast Carcinomas
Author(s)Rashidian, Mohammad; Bagnato, Aaron; Dongre, Anushka; Reinhardt, Ferenc; Keckesova, Zuzana; Ploegh, Hidde; Weinberg, Robert A; ... Show more Show less
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The epithelial-to-mesenchymal transition (EMT) is a cell biological program that confers mesenchymal traits on carcinoma cells and drives their metastatic dissemination. It is unclear, however, whether the activation of EMT in carcinoma cells can change their susceptibility to immune attack. We demonstrate here that mammary tumor cells arising from more epithelial carcinoma cell lines expressed high levels of MHC-I, low levels of PD-L1, and contained within their stroma CD8þT cells and M1 (antitumor) macrophages. In contrast, tumors arising from more mesenchymal carcinoma cell lines exhibiting EMT markers expressed low levels of MHC-I, high levels of PD-L1, and contained within their stroma regulatory T cells, M2 (protumor) macrophages, and exhausted CD8þT cells. Moreover, the more mesenchymal carcinoma cells within a tumor retained the ability to protect their more epithelial counterparts from immune attack. Finally, epithelial tumors were more susceptible to elimination by immunotherapy than corresponding mesenchymal tumors. Our results identify immune cells and immunomodulatory markers that can be potentially targeted to enhance the susceptibility of immunosuppressive tumors to various therapeutic regimens.
DepartmentLudwig Center for Molecular Oncology; Massachusetts Institute of Technology. Department of Biology
American Association for Cancer Research (AACR)
Dongre, Anushka, et al. “Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast Carcinomas.” Cancer Research 77, 15 (April 2017): 3982–3989 © 2017 American Association for Cancer Research
Author's final manuscript