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Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2022; 28(27): 3297-3313
Published online Jul 21, 2022. doi: 10.3748/wjg.v28.i27.3297
Tumor microenvironment in pancreatic ductal adenocarcinoma: Implications in immunotherapy
Caitlyn Smith, Wei Zheng, Jixin Dong, Yaohong Wang, Jinping Lai, Xiuli Liu, Feng Yin
Caitlyn Smith, Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, United States
Wei Zheng, Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, United States
Jixin Dong, Eppley Institute for Research in Cancer and Allied Diseases, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, United States
Yaohong Wang, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, United States
Jinping Lai, Department of Pathology and Laboratory Medicine, Kaiser Permanente Sacramento Medical Center, Sacramento, CA 95825, United States
Xiuli Liu, Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, United States
Feng Yin, Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65212, United States
Author contributions: Smith C and Yin F collected and analyzed the data, made the tables and figure, wrote and finalized the manuscript; Zheng W, Dong J, Wang Y, Lai J and Liu X critically reviewed the manuscript; and All authors have approved the final manuscript.
Conflict-of-interest statement: The authors declare no competing interests in this study.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng Yin, MD, PhD, Assistant Professor, Department of Pathology and Anatomical Sciences, University of Missouri, One Hospital Drive, MSB M263, Columbia, MO 65212, United States. fengyin@health.missouri.edu
Received: January 16, 2022
Peer-review started: January 16, 2022
First decision: April 11, 2022
Revised: April 22, 2022
Accepted: June 19, 2022
Article in press: June 19, 2022
Published online: July 21, 2022
Abstract

Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers. Surgical resection is the only curable treatment option, but it is available for only a small fraction of patients at the time of diagnosis. With current therapeutic regimens, the average 5-year survival rate is less than 10% in pancreatic cancer patients. Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage. However, its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer. Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug efficacy in pancreatic cancer. In this review, we discuss the role of the tumor microenvironment in pancreatic cancer and the latest advances in immunotherapy on pancreatic cancer.

Keywords: Pancreatic ductal adenocarcinoma, Tumor microenvironment, Immunotherapy, Clinical trial, Chemotherapy, Treatment

Core Tip: Despite advances in basic and translational research, pancreatic cancer remains one of the most lethal cancers. Recent breakthroughs in immunotherapy have revolutionized cancer therapy and have shown great potential to transform pancreatic cancer treatment. However, due to the barrier related to the tumor microenvironment, pancreatic cancer has shown inferior treatment outcomes toward various immunotherapy regimens. Further efforts, such as combinatory immunotherapy or molecular tumor subtyping, are warranted to overcome immunotherapy resistance in pancreatic cancer.