Defining the role of IL-1α in head and neck squamous cell carcinoma 3641

Abstract Description Inflammation drives cancer progression, with inflammatory cells and mediators shaping the tumor microenvironment (TME). However, the inflammatory drivers from tumor cells and the innate immune system that foster an immunosuppressive TME remain unclear. To address this, I use a mouse model of head and neck squamous cell carcinoma (HNSCC) with the indolent MOC1 and aggressive MOC2 cell lines. Preliminary studies reveal that MOC2 tumors exhibit elevated expression of interleukin-1 alpha (IL-1α) both in vivo and in vitro, and blocking IL-1α significantly slows tumor growth. IL-1α, a potent pro-inflammatory cytokine, mediates chronic inflammation and is produced by barrier and myeloid cells under homeostatic conditions. Our findings indicate that MOC2 tumor cells establish an IL-1α-driven feedforward loop that increases tumor growth and proliferation. Co-culture experiments reveal IL-1α-mediated interactions with tumor-associated macrophages (TAMs) that drive an immunosuppressive TME. This study highlights the critical role of tumor-derived IL-1α in fostering immunosuppressive conditions within the TME and its potential as a therapeutic target. Understanding the drivers and downstream effects of IL-1α signaling provides valuable insights into tumor-myeloid crosstalk, advancing cancer immunobiology and therapeutic strategies. Funding Sources Supported by T32AI007019-50 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)