Abstract 3963: Deep serial analysis of the TCR/BCR CDR3 adaptome repertoire in peripheral blood of pancreatic cancer patients in a randomized study of neoadjuvant chemotherapy with or without autophagy inhibition

Abstract

Abstract Pancreatic cancer has a paucity of dendritic cells and almost no T lymphocytes. Here, we used Next Generation Sequencing following dimer avoidance multiplexed PCR (DAM-PCR) immune repertoire to study the characteristics and diversity of the TCR repertoire among PDAC (Pancreatic Ductal Adenocarcinoma) patients who underwent chemotherapy with or without Hydroxycholoroquine followed by surgical extirpation. We sequenced the TCR α,β,γ, and δ chains and the B-cell receptor (BCR) heavy chain (IgH) complementary-determining region 3 (CDR3) repertoire in peripheral blood mononuclear cells (PBMCs) from 10 PDAC patients before (Pre-chemo) and after chemotherapy (Post-chemo) and following operation (Postop). The distribution of CDR3, VD indel, and DJ indel lengths were similar among the Prechemo, Postchemo and Postop groups. The TCR repertoire diversity of PDAC patients was much lower compared to healthy donors (HD). The diversity index (D50) of TCR α and β’s in PDAC patients who received HCQ during chemotherapy was less than in patients without HCQ (p<.05). TRBV expression increased and some public sequences diminished at individual time points following chemotherapy and postop. Full analysis of an ongoing study will be presented. Citation Format: Yue Wang, Michael T. Lotze. Deep serial analysis of the TCR/BCR CDR3 adaptome repertoire in peripheral blood of pancreatic cancer patients in a randomized study of neoadjuvant chemotherapy with or without autophagy inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3963.