Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy

• Type of Material: Article
• Authors: Matthew R. Farren, Emory University; Layal Sayegh, Emory University; Michael Brandon Ware, Emory University; Hsiao-Rong Chen, Emory University; Jingjing Gong, NanoString Inc.; Yan Liang, NanoString Inc.; Alyssa Krasinskas, Emory University; Shishir Maithel, Emory University; Mohammad Zaidi, Emory University; Juan Sarmiento, Emory University; David Kooby, Emory University; Pretesh Patel, Emory University; Bassel El-Rayes, Emory University; Walid Shaib, Emory University; Gregory Lesinski, Emory University
• Language: English
• Date: 2020-01-16
• Publisher: The American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2020, American Society for Clinical Investigation.
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.130362
• Title of Journal or Parent Work: JCI Insight
• Volume: 5
• Issue: 1
• Start Page: 1
• End Page: 14
• Grant/Funding Information: Research reported in this publication was supported in part by the EIGC Shared Resource and the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/National Cancer Institute under award P30CA138292.; We would like to acknowledge the contribution of the EIGC, which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities.; This work was funded in part by in-kind grant support (materials and lab services) from NanoString Inc. as well as research funds from the Hirshberg Foundation and NIH grants R01 CA208253 and R01228406.
• Keywords: Medicine, Research & Experimental; Set enrichment analysis; Research & Experimental Medicine; Science & Technology; Database; Life Sciences & Biomedicine; Cells
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology; Biology, Bioinformatics; Health Sciences, Oncology

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has dismal 5-year survival (<9%). We hypothesize that exposure of tumors to conventional therapies may preferentially modulate immune biomarkers in the tumor microenvironment in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. Total expression of immunologically relevant transcripts and spatially resolved expression of immunologically relevant proteins was quantitated using multiplexed methods (NanoString nCounter and GeoMX platforms). This analysis identified numerous differentially expressed transcripts associated with the type of neoadjuvant therapy received. Moreover, we identified significant alterations in the expression and/or spatial distribution of immunologically relevant proteins in different regions (tumor cell rich, immune cell rich, stromal cell rich) of the tumor microenvironment. These data provide insight into the immunological effects of clinically relevant neoadjuvant therapy for resectable/borderline-resectable PDAC by describing significant differences in the expression of key immunologic biomarkers within the PDAC microenvironment that were associated with the type of treatment patients received prior to surgical resection. This represents a comprehensive analysis of numerous biomarkers conducted on the PDAC microenvironment. This work may guide strategic new combination therapies for pancreatic cancer.