Thesis, FRANZEN Rachelle

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, driven by profound immunosuppression and a highly resistant tumor microenvironment. This thesis explores whether regulating tRNA modifications through ELP3 loss can reshape antigen presentation and enhance anti‑tumor immunity. Building on previous findings, I investigated how ELP3 deletion affects PDAC cell behavior, tumor development, and interactions with the immune system, including the characterization of major immune‑cell populations. I examined the accumulation and processing of U34‑derived protein aggregates, and the resulting modulation of MHC‑II expression and IFN‑γ responsiveness. Together, this work highlights how altering tRNA‑modification pathways can influence antigen presentation in PDAC and may offer new avenues to stimulate CD4⁺ T‑cell-mediated anti‑tumor responses.