Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2021; 27(40): 6775-6793
Published online Oct 28, 2021. doi: 10.3748/wjg.v27.i40.6775
Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer
Lorena Ostios-Garcia, Julia Villamayor, Esther Garcia-Lorenzo, David Vinal, Jaime Feliu
Lorena Ostios-Garcia, Julia Villamayor, Esther Garcia-Lorenzo, David Vinal, Jaime Feliu, Department of Oncology, La Paz University Hospital, IDIPAZ, CIBERONC, Cátedra UAM-AMGEN, Madrid 28046, Spain
Author contributions: Ostios-Garcia L performed the review, wrote the manuscript and reviewed the data; Villamayor J and Garcia-Lorenzo E helped write the manuscript; Vinal D and Feliu J reviewed the data.
Supported by the Instituto de Salud Carlos III, Ministerio de Economia, Industria y Competitividad, No. PI18/01604.
Conflict-of-interest statement: Authors declare no conflict of interest for this manuscript.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jaime Feliu, MD, PhD, Associate Professor, Chief Physician, Department of Oncology, La Paz University Hospital, IDIPAZ, CIBERONC, Cátedra UAM-AMGEN, Paseo de la Castellana, 261, Madrid 28046, Spain. jaimefeliu@hotmail.com
Received: February 23, 2021
Peer-review started: February 23, 2021
First decision: June 14, 2021
Revised: June 28, 2021
Accepted: September 19, 2021
Article in press: September 19, 2021
Published online: October 28, 2021
Processing time: 245 Days and 14.9 Hours
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with high lethality. Even with surgery, radiotherapy, chemotherapy, and other locoregional or systemic therapies, the survival rates for PDAC are low and have not significantly changed in the past decades. The special characteristics of the PDAC’s microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this disease. PDAC is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T cells. The pancreatic microenvironment is a fibrotic, microvascularized stroma that isolates the tumor from systemic vascularization. Immunotherapy, a novel approach that has demonstrated effectiveness in certain solid tumors, has failed to show any practice-changing results in pancreatic cancer, with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden, which show prolonged survival rates with immunotherapy. Currently, numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell transfer, alone or in combination with other immunotherapeutic agents, chemoradiotherapy, and other targeted therapies. A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.

Keywords: Pancreatic cancer; Immunity; Immune evasion; Tumor microenvironment; Immunotherapy; Cancer vaccines

Core Tip: Immunotherapy has demonstrated effectiveness in treating several solid tumors and has become a major revolution in oncology. In pancreatic ductal adenocarcinoma, however, the outcomes continue to be poor due to its special immune response and microenvironmental characteristics. In this review, we summarize the most important concepts of the immune system and the current landscape of immunotherapy in pancreatic cancer.