Dakota Reinartz Contribution of an innate immune sensor on Head and Neck Squamous Cell Carcinoma (HNSCC) The role of the intracellular pattern recognition receptor AIM2 in inflammation associated cancersremains unclear. Preliminary data suggests that Aim2-/- mice treated with the oral carcinogen 4NQOcontinuously as an experimental model of HNSCC display larger tumors heightened IFN and increasedrecruitment of draining lymph node IFN-positive CD4 and CD8 T cells compared to wild type counterparts.RNA sequencing of whole tissue RNA revealed an enrichment of IFN-stimulated genes in 4NQO-treatedAim2-/- mice further suggesting AIM2 restricts IFN. Interestingly removal of 4NQO lead to enhanced tissueIl10 in Aim2-/- mice which required with hematopoietic expression of AIM2 in vivo. Consistent with thesefindings preliminary data indicates in vitro Th1-differented Aim2-/- CD4 T cells produce more IFN and IL-10than wild type controls. We hypothesize that AIM2 restricts HNSCC growth by preventing the switch from CD4T cell production of pro-inflammatory IFN to immunosuppressive IL-10. To address this hypothesis first wewill determine the molecular mechanism by which AIM2 modulates the IFN and IL-10 balance in Th1 CD4 Tcells. Second we will determine the mechanism and cellular contribution by which AIM2 restricts HNSCCdevelopment in vivo. Our proposed research will uncover the molecular and cellular mechanisms by whichAIM2 and inflammation drive HNSCC which could identify targets for novel therapeutics or preventativescreens while also defining a novel biological function for AIM2 in shaping adaptive immunity.