Abstract 3922: Quaking modulates anti-tumor immunity by regulating antigen processing and presentation in dendritic cells

Abstract

Abstract Dendritic cells are essential players in anti-tumor immunity. One of their critical roles is to process and present tumor associated antigens to T cells, thereby inducing antigen-specific T cell response. However, cellular factors and molecular pathways regulating antigen processing and presentation by DCs are not fully understood.Here, we revealed a potential regulatory role of a transcriptional co-activator, Quaking (QKI), and its binding partner, PPARδ in antigen processing and presentation by DCs. Consistent with our previous studies in neural stem cells and microglia, we found QKI and PPARδ enhance phagocytosis in DCs by upregulating genes involved in the formation of phagosome and endosomes. QKI- or PPARδ-deficient DCs showed reduced CD8+ T cell priming capacity in vitro. In vivo tumor models suggested DC-specific knocking out of QKI or PPARδ promoted the tumor growth. Furthermore, ablation of QKI or PPARδ in DCs limited the effectiveness of immune checkpoint blockade in multiple tumor models.Together, these revealed a transcriptional regulation of antigen processing and presentation by DCs through QKI and PPARδ. Our data also suggested that perturbing this important function of DC would subvert their anti-tumor activity, highlighting the pivotal role of DCs in an effective anti-tumor immune response. Citation Format: Yating Li, Jian Hu, Cassian Yee. Quaking modulates anti-tumor immunity by regulating antigen processing and presentation in dendritic cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3922.