Exploring epithelial cell mitophagy as an inducer of adaptive immunity (E05*)

探索上皮细胞线粒体自噬作为适应性免疫诱导剂 (E05*)

• 批准号: 432221897
• 金额: --
• 依托单位: Georg-Speyer-Haus, Institut für Tumorbiologie und experimentelle Therapie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/432221897?language=en
• 关键词: Exploring; epithelial; cell; mitophagy; inducer

In a model of intestinal tumorigenesis, we recently found that absence of STAT3 resulted in elevated mitophagy in intestinal epithelial cells (IEC), which in turn led to lysosomal membrane permeabilization (LMP), thereby enhancing antigen presentation and activation of CD8+ T cells. In this proposal, we plan to define the molecular mechanisms that trigger mitophagy and to screen for inducers of mitophagy that subsequently initiate LMP. Furthermore, we will evaluate whether mitophagy and LMP induction is capable of sensitizing established tumors to checkpoint inhibition and will examine whether mitophagy and LMP induction represents a common mechanism to enhance CD8+T cell activation.

在肠道肿瘤发生模型中，我们最近发现STAT3的缺失会导致肠上皮细胞（IEC）的线粒体自噬升高，进而导致溶酶体膜透化（LMP），从而增强抗原呈递和CD8+ T细胞的激活。在本提案中，我们计划定义触发线粒体自噬的分子机制，并筛选随后启动 LMP 的线粒体自噬诱导剂。此外，我们将评估线粒体自噬和 LMP 诱导是否能够使已建立的肿瘤对检查点抑制敏感，并将检查线粒体自噬和 LMP 诱导是否代表增强 CD8+T 细胞活化的常见机制。