Abstract B31: IRAK-4 signaling in melanoma contributes to reduced expression of inflammatory factors in vitro while contributing to tumor growth in vivo

An underlying and universal hindrance to T-cell-based cancer therapies is the development of immunosuppressive mechanisms that in large part originate from the persistent expression of inflammatory factors. Understanding the fundamental mechanisms that regulate chronic inflammation and targeting of this pathway(s) is critical for developing effective strategies to restore anti-tumor T-cell activity. We recently reported that the IL-1 receptor associated kinase-4 (IRAK-4) is over-expressed and activated in most melanoma cases. IRAK-4 is a central kinase in the inflammatory process that regulates the expression of various inflammatory and immunosuppressive molecules. Inhibiting IRAK-4 activity in melanoma drastically reduced the expression of various inflammatory factors in vitro. Furthermore, IRAK-4 signaling in melanoma contributed to tumor growth in vivo and was associated with an increased frequency of phenotypically exhausted (PD1 + Lag3 + ) tumor infiltrating T-cells, myeloid derived suppressor cells, and a trend toward higher numbers of CD4 + T regs. Ongoing studies are focused on testing the hypothesis that targeting IRAK-4 signaling in tumor cells will alter the expression of inflammatory factors in the tumor environment which will reduce immunosuppression and sensitize melanoma to T-cell-mediated killing. Citation Format: Jackline Joy Martin Lasola, Degui Geng, Rojesh Shrestha, Eduardo Davila. IRAK-4 signaling in melanoma contributes to reduced expression of inflammatory factors in vitro while contributing to tumor growth in vivo. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B31.