Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes

Cancer Research
Cristina GhirelliVassili Soumelis

Abstract

Reciprocal interactions between tumor cells and their microenvironment vitally impact tumor progression. In this study, we show that GM-CSF produced by primary breast tumor cells induced the activation of plasmacytoid predendritic cells (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF receptor were increased in breast tumors compared with noninvolved adjacent breast tissue. Tumor-activated pDC acquired naïve CD4(+) T-cell stimulatory capacity and promoted a regulatory Th2 response. Finally, the concomitant increase of GM-CSF and pDC was significantly associated with relatively more aggressive breast cancer subtypes. Our results characterize the first tumor-derived factor that can activate pDC to promote a regulatory Th2 response, with implications for therapeutic targeting of a tumor-immune axis of growing recognition in its significance to cancer.

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Citations

Jan 16, 2016·Journal of Mammary Gland Biology and Neoplasia·Tanu SharmaChandi C Mandal
Apr 28, 2016·Pharmacology & Therapeutics·Jose R Conejo-GarciaJuan R Cubillos-Ruiz
Sep 14, 2016·Oncoimmunology·Cristina GhirelliVassili Soumelis
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Jan 10, 2018·Immunology·Matthew Collin, Venetia Bigley
Apr 25, 2019·PLoS Biology·Salvatore RaieliVassili Soumelis
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Feb 15, 2018·Seminars in Cell & Developmental Biology·Solana AlculumbreVassili Soumelis

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