Dissertations and Theses (Open Access)

Author ORCID Identifier

https://orcid.org/0000-0002-3245-9129

Date of Graduation

8-2026

Document Type

Dissertation (PhD)

Program Affiliation

Immunology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Cassian Yee

Committee Member

Jian Hu

Committee Member

Stephanie Watowich

Committee Member

Yejing Ge

Committee Member

Matthew Gubin

Abstract

Dendritic cells are essential players in the anti-tumor immunity. One of their critical roles is to process and present tumor associated antigens to naïve 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 regulatory role of an RNA-binding protein, Quaking, and its binding partner, PPARβ in antigen processing and presentation by DCs. We found that QKI and PPARβ enhanced phagocytosis in DCs by regulating genes involved in the formation of phagosome and endosomes. QKI- or PPARβ-deficient DCs showed reduced CD8+ T cell priming capacity in vitro. DC-specific knockout of QKI or PPARβ promoted tumor growth in syngeneic mouse models. Furthermore, ablation of QKI or PPARβ in DCs limited the response of tumors to immune checkpoint blockade. Moreover, our data showed that QKI expression was suppressed in the tumor microenvironment, revealing the downregulation of QKI as a novel tumor immune escape mechanism employed by tumor cells. Together, our results revealed a pivotal role of QKI and PPARβ in antigen processing and presentation by DCs in the anti-tumor immune responses, which could lead to new strategies target DCs for improving cancer immunotherapy.

Keywords

Dendritic cells; Tumor immunology; Antigen presentation

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Available for download on Friday, August 06, 2027

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