A tumor-myeloid cell axis, mediated via the cytokines IL-1α and TSLP, promotes the progression of breast cancer.

Tumors actively manipulate the immune response through the production of factors that attract immune cells and subsequently alter their ability to recognize and effectively remove the tumor. While this mechanism for evading the immune system is an important aspect of tumor survival, the factors that serve as primary growth factors for the tumor are less understood. Here we demonstrate a previously unknown mechanism by which breast-cancer cells manipulate tumor-infiltrating myeloid cells to maintain their survival. Tumor-derived interleukin 1α (IL-1α), acting on infiltrating myeloid cells, induced the expression of a critical tumor survival factor, the cytokine TSLP. TSLP promoted the survival of the tumor cells through induction of the expression of the anti-apoptotic molecule Bcl-2. TSLP signaling was also required for metastasis to the lungs. These studies define a novel IL-1α-TSLP-mediated crosstalk between tumor-infiltrating myeloid cells and tumor cells in the control of metastatic breast cancer.