Breast cancer cell-derived GM-CSF licenses regulatory Th2 induction by plasmacytoid pre-dendritic cells in aggressive disease subtypes

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 pre-dendritic cells (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF receptor were increased in breast tumors compared to non-involved adjacent breast tissue. Tumor-activated pDC acquired naive CD4+ T cell stimulatory capacity and promoted a regulatory Th2 response. Lastly, 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.