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

项目总结 免疫检查点阻断已被证明是治疗头颈癌的一种有效方法 (HNC)患者。然而，超过85%的患者无法从这一策略中受益，这主要是由于高度 已确诊癌症的免疫抑制肿瘤微环境(TME)。口腔白斑/口腔上皮 发育不良(OED)先于HNC，为根除疾病提供了独特的时间窗口。然而，外科手术 切除口腔面部会导致严重的并发症和功能丧失，更重要的是，不能 逆野癌变。尽管有警惕的后续行动，OEDs的一部分仍会转化为恶性肿瘤。频密 免疫细胞渗透是OEDs的一个共同特征，然而，对OEDs的时间和方式知之甚少 逃避免疫监控，走上不归路。通过家长奖的支持，我们 构建了独特的基因工程小鼠模型，可以模拟一系列OED/HNC病变 在组织学和免疫表型上与人类疾病高度相似。在本补编中，有两个 免疫肿瘤学翻译网络内的免疫预防小组将整合最近的 开发用于单细胞RNA-Seq数据集的免疫图谱分析流水线以评估预防 一种新的组合的效果，旨在缓解抑制性髓系细胞的早期扩张，并 丰富效应者的CD4+T细胞。通过补充开发的新技术将加强这两项 为遗传性高风险OEDs提供新的有前景的免疫预防资产的母公司项目和信息。

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.