Gemcitabine improves tumor antigen presentation in pancreatic cancer.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B151
Abstract ID: 5387

Presenting Author:
Alaina C Larson , Graduate Student at Univ. of Nebraska Med. Ctr.

Abstract:

Pancreatic cancer has a 5-year overall survival rate of only 12%, and there is a critical need to improve therapeutic strategies for patients. Gemcitabine is a chemotherapy used for this disease, and it has immunomodulatory features that are not yet well understood. We sought to characterize the impact of gemcitabine on human leukocyte antigen class I (HLA-I), which presents antigenic peptides to T cells to trigger their lysis of cancer cells. The central hypothesis tested in this study is that gemcitabine influences HLA-I molecules in a multi-regulatory fashion to improve tumor antigen presentation by pancreatic cancer cells. Gemcitabine-induced changes in HLA-I expression and function were assayed for a panel of human pancreatic cancer cells, using qRT-PCR and flow cytometry. Brefeldin A assays were used to monitor variance in HLA-I surface stability following gemcitabine exposure. HLA-bound peptides were isolated and sequenced, and their binding affinity and induction of T cell reactivity were evaluated by computational approaches. Gemcitabine increased mRNA transcripts, surface presence, and surface stability of HLA-I molecules by pancreatic cancer cells, and the HLA-bound peptidome after gemcitabine treatment demonstrated presentation of unique peptides with predicted stronger affinity and immunogenicity. These phenotypes suggest gemcitabine has potential as a priming mechanism to enhance immunotherapy efficacy and optimize vaccination strategies in pancreatic cancer.