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Epithelial-to-Mesenchymal TransitionContributes toImmunosuppression inBreast Carcinomas Anushka DongreMohammad RashidianFerenc Reinhardt2017 год

Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast Carcinomas
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Аннотация: Abstract 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 CD8+ T 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 CD8+ T 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. Cancer Res; 77(15); 3982–9. ©2017 AACR.
Год издания: 2017
Авторы: Anushka Dongre, Mohammad Rashidian, Ferenc Reinhardt, Aaron Bagnato, Zuzana Keckesova, Hidde L. Ploegh, Robert A. Weinberg
Издательство: American Association for Cancer Research
Источник: Cancer Research
Ключевые слова: Cancer Immunotherapy and Biomarkers, Cancer Cells and Metastasis, Immunotherapy and Immune Responses
Другие ссылки: Cancer Research (HTML)
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