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

达科塔·雷纳茨 先天性免疫传感器在头颈部鳞状细胞癌中的作用 细胞内模式识别受体AIM 2在炎症相关癌症中的作用 仍不清楚初步数据表明，口服致癌物4 NQO治疗的Aim 2-/-小鼠 持续作为HNSCC的实验模型显示更大的肿瘤，IFNγ升高， 与野生型对应物相比，引流淋巴结IFNγ阳性CD 4和CD 8 T细胞的募集。 全组织RNA的RNA测序显示IFNγ刺激的基因在4 NQO处理的小鼠中富集。 Aim 2-/-小鼠，进一步表明AIM 2限制IFNγ。有趣的是，去除4 NQO导致增强的组织 IL 10在Aim 2-/-小鼠中的表达，这需要AIM 2在体内的造血表达。符合这些 初步数据表明，体外Th 1分化的Aim 2-/-CD 4 T细胞产生更多的IFNγ和IL-10 比野生型对照组更好。我们假设AIM 2通过阻止CD 4+细胞的转换来限制HNSCC的生长。 T细胞产生促炎性IFNγ至免疫抑制性IL-10。为了解决这个问题，我们首先 将确定AIM 2调节Th 1 CD 4 T细胞中IFNγ和IL-10平衡的分子机制。 细胞其次，我们将确定AIM 2限制HNSCC的机制和细胞贡献 体内发育我们提出的研究将揭示分子和细胞机制， AIM 2和炎症驱动HNSCC，这可以确定新的治疗或预防靶点 筛选，同时还定义了AIM 2在形成适应性免疫方面的新生物学功能。

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.