REVIEW
How to overcome resistance to immune checkpoint inhibitors in colorectal cancer: From mechanisms to translation
Qianyu Wang,
Xiaofei Shen,
Gang Chen,
Junfeng Du,
Qianyu Wang
Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China
The Second School of Clinical Medicine, Shanxi Medical University, Taiyuan, China
Search for more papers by this authorXiaofei Shen
Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Search for more papers by this authorCorresponding Author
Gang Chen
Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China
Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, China
Correspondence
Junfeng Du and Gang Chen, Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, No. 5, Nanmen Cang, Beijing 100700, China.
Email: [email protected] (J. D.) and [email protected] (G. C.)
Search for more papers by this authorCorresponding Author
Junfeng Du
Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China
Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, China
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
Correspondence
Junfeng Du and Gang Chen, Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, No. 5, Nanmen Cang, Beijing 100700, China.
Email: [email protected] (J. D.) and [email protected] (G. C.)
Search for more papers by this authorQianyu Wang,
Xiaofei Shen,
Gang Chen,
Junfeng Du,
Qianyu Wang
Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China
The Second School of Clinical Medicine, Shanxi Medical University, Taiyuan, China
Search for more papers by this authorXiaofei Shen
Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
Search for more papers by this authorCorresponding Author
Gang Chen
Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China
Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, China
Correspondence
Junfeng Du and Gang Chen, Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, No. 5, Nanmen Cang, Beijing 100700, China.
Email: [email protected] (J. D.) and [email protected] (G. C.)
Search for more papers by this authorCorresponding Author
Junfeng Du
Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China
Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, China
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
Correspondence
Junfeng Du and Gang Chen, Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, No. 5, Nanmen Cang, Beijing 100700, China.
Email: [email protected] (J. D.) and [email protected] (G. C.)
Search for more papers by this authorQianyu Wang and Xiaofei Shen contributed equally to this study.
Abstract
Immunotherapy, especially with immune checkpoint inhibitors (ICIs), has shown advantages in cancer treatment and is a new hope for patients who have failed multiline therapy. However, in colorectal cancer (CRC), the benefit is limited to a small subset of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic CRC (mCRC). In addition, 45% to 60% of dMMR/MSI-H mCRC patients showed primary or acquired resistance to ICIs. This means that these patients may have potential unknown pathways mediating immune escape. Almost all mismatch repair-proficient (pMMR) or microsatellite-stable (MSS) mCRC patients do not benefit from ICIs. In this review, we discuss the mechanisms of action of ICIs and their current status in CRC. We then discuss the mechanisms of primary and acquired resistance to ICIs in CRC. Finally, we discuss promising therapeutic strategies to overcome resistance to ICIs in the clinic.
Graphical Abstract
CONFLICT OF INTEREST STATEMENT
The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.
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