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 IFN¿ and increased
recruitment 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-treated
Aim2-/- mice, further suggesting AIM2 restricts IFN¿. 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 IFN¿ 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 IFN¿ to immunosuppressive IL-10. To address this hypothesis, first we
will determine the molecular mechanism by which AIM2 modulates the IFN¿ 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.