Review
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2023; 15(2): 240-250
Published online Feb 15, 2023. doi: 10.4251/wjgo.v15.i2.240
“Cold” colorectal cancer faces a bottleneck in immunotherapy
Jia-Liang Liu, Ming Yang, Jun-Ge Bai, Zheng Liu, Xi-Shan Wang
Jia-Liang Liu, Ming Yang, Jun-Ge Bai, Zheng Liu, Xi-Shan Wang, Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China
Author contributions: Liu JL, Yang M, Bai JG contributed equally to this work in all aspects of conceptualization, design, drafting and writing of the manuscript, research and analysis, and providing approval of the final version.
Conflict-of-interest statement: The authors state that they have no conflicts of interest to declare.
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: Zheng Liu, FASCRS, MD, PhD, Professor, Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. zheng.liu@cicams.ac.cn
Received: September 22, 2022
Peer-review started: September 22, 2022
First decision: November 30, 2022
Revised: December 18, 2022
Accepted: January 5, 2023
Article in press: January 5, 2023
Published online: February 15, 2023
Processing time: 145 Days and 8.5 Hours
Abstract

The advent of immunotherapy and the development of immune checkpoint inhibitors (ICIs) are changing the way we think about cancer treatment. ICIs have shown clinical benefits in a variety of tumor types, and ICI-based immunotherapy has shown effective clinical outcomes in immunologically “hot” tumors. However, for immunologically “cold” tumors such as colorectal cancer (CRC), only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates. In this review, we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC, and summarize the treatment strategies and challenges of immunotherapy for cold CRC. We also explain the mechanism, biology, and role of immunotherapy for cold CRC, which will help clarify the future development of immunotherapy for cold CRC and discovery of more emerging strategies for the treatment of cold CRC.

Keywords: Immunotherapy; “Cold” colorectal cancer; Immune checkpoint inhibitors; Cancer treatment; Review

Core Tip: Immune checkpoint inhibitors (ICIs) are usually produced by antibodies, and their effectiveness relies on the antitumor effects of immune cells (especially T cells). Colorectal cancer (CRC) is one of the most common forms of cancer worldwide. Only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates. In this review, we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC, and summarize the treatment strategies and challenges of immunotherapy for cold CRC.