Enhance Immunoprevention by Blocking Early Expansion of Suppressive Myeloid Cells - Supplement Proposal

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

PROJECT SUMMARY Immune checkpoint blockade has proven an effective treatment for a subset of head and neck cancer (HNC) patients. However, over 85% of the patients cannot benefit from this strategy, largely due to the highly immunosuppressive tumor microenvironment (TME) in established cancers. Oral leukoplakias / Oral Epithelial Dysplasias (OEDs) precede HNC and offer a unique time window for disease eradication. However, surgical resection in the orofacial region results in significant morbidity and function loss, and more importantly, cannot reverse field cancerization. A subset of OEDs transform into malignancy despite vigilant follow-ups. Frequent immune cell infiltration is a common feature of OEDs, however, little is known about when and how OEDs evade from immuno-surveillance and reach a point-of-no-return. Through the support of the parent award, we constructed unique genetically engineered mouse models, which can model a spectrum of OED/HNC lesions with high-fidelity histologic and immunophenotypic resemblance to human diseases. In this supplement, two immunoprevention teams within the Immuno-Oncology Translational Network will integrate a recently developed immune profiling analytical pipeline for single-cell RNA-Seq data sets to assess the prevention effects of a novel combination, which aims to mitigate the early expansion of suppressive myeloid cells and to enrich effector CD4+ T-cells. The new technologies developed through the supplement will strengthen the two parent projects and inform new promising immunoprevention assets for genetically high-risk OEDs.