Comparison of Shared Class I HLA-bound Non-canonical Neoepitopes between Normal and Neoplastic Tissues of Pancreatic Adenocarcinoma.

Abstract

Purpose: Developing T cell or vaccine therapies for pancreatic ductal adenocarcinoma (PDAC) has been challenging due to a lack of knowledge regarding immunodominant, cancer-specific antigens, as a scarcity of genomic mutation-associated neoepitopes characterizes PDAC and there are limited availability of effective approaches to discover them.

Experimental design: We utilized an advanced mass spectrometry approach to compare the immunopeptidome of PDAC tissues and matched normal tissues from the same patients.

Results: We identified HLA class I-binding variant peptides derived from canonical proteins, which had single amino-acid substitutions not attributed to genetic mutations or RNA editing. These amino-acid substitutions appeared to result from translational errors. The variant peptides were predominantly enriched in tumor tissues, with some peptides shared across patients. Importantly, several of these variant peptides were more immunogenic than their wild-type counterparts.

Conclusions: The shared non-canonical neoepitopes identified in this study offer promising candidates for vaccine and T cell therapy development, potentially providing new avenues for immunotherapy in PDAC.