Contribution of Innate Immune Sensing on Head and Neck Squamous Cell Carcinoma (HNSCC)

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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 cancers remains unclear. Preliminary data suggests that Aim2-/- mice treated with the oral carcinogen 4NQO continuously as an experimental model of HNSCC display larger tumors, heightened IFNγ and increased recruitment of draining lymph node IFNγ-positive CD4 and CD8 T cells compared to wild type counterparts. RNA sequencing of whole tissue RNA revealed an enrichment of IFNγ-stimulated genes in 4NQO-treated Aim2-/- mice, further suggesting AIM2 restricts IFNγ. Interestingly, removal of 4NQO lead to enhanced tissue Il10 in Aim2-/- mice, which required with hematopoietic expression of AIM2 in vivo. Consistent with these findings, preliminary data indicates in vitro Th1-differented Aim2-/- CD4 T cells produce more IFNγ and IL-10 than wild type controls. We hypothesize that AIM2 restricts HNSCC growth by preventing the switch from CD4 T cell production of pro-inflammatory IFNγ to immunosuppressive IL-10. To address this hypothesis, first we will determine the molecular mechanism by which AIM2 modulates the IFNγ and IL-10 balance in Th1 CD4 T cells. Second, we will determine the mechanism and cellular contribution by which AIM2 restricts HNSCC development in vivo. Our proposed research will uncover the molecular and cellular mechanisms by which AIM2 and inflammation drive HNSCC, which could identify targets for novel therapeutics or preventative screens, while also defining a novel biological function for AIM2 in shaping adaptive immunity.