Research progress on the mechanisms of immunotherapy resistance in microsatellite-stabilized colorectal cancer
10.12354/j.issn.1000-8179.2025.20250764
- VernacularTitle:微卫星稳定型结直肠癌免疫治疗耐药机制的研究进展
- Author:
Zhang JIAQI
1
;
Li SHENGWEN
1
Author Information
1. 山西医科大学附属山西省人民医院肿瘤科(太原市 030012)
- Publication Type:Journal Article
- Keywords:
colorectal cancer(CRC);
microsatellite-stabilized(MSS)type;
drug resistance;
tumor microenvironment;
metabolic repro-gramming
- From:
Chinese Journal of Clinical Oncology
2025;52(17):910-916
- CountryChina
- Language:Chinese
-
Abstract:
Colorectal cancer(CRC),a common malignant tumor of the digestive system,poses a significant threat to patients'quality of life and prognosis.In recent years,immune checkpoint inhibitor(ICI)therapy has brought breakthroughs for patients with deficient mismatch re-pair(dMMR)or microsatellite instability-high(MSI-H)types of CRC.However,the efficacy of ICI therapy in patients with microsatellite stabil-ity(MSS)CRC,who account for more than 85%of all CRCs,is significantly limited,which is a clinical dilemma that highlights the importance of in-depth investigation of immunotherapy resistance mechanisms.Existing studies have demonstrated that the microenvironment of MSS-type CRC is characterized by unique immunosuppression,including multidimensional factors,such as defective antigen presentation,infiltra-tion of suppressive immune cells,and dysregulation of the cytokine network.These factors collectively constitute a response barrier to im-munotherapy.This review systematically analyzes the key molecular mechanisms of immunoresistance in MSS-type CRC,focusing on the im-munosuppressive characteristics of the tumor microenvironment,epigenetic regulatory abnormalities,immune-metabolic reprogramming,gut microbiota imbalance,and other core aspects.The study aims to provide a theoretical basis for breaking through the immunothera-peutic bottleneck of MSS-type intestinal cancer at the mechanistic level and pointing to the potential direction of research on combined therapeutic strategies.
