Advances in Research on Mechanisms of Resistance to Immune Checkpoint Inhibitors
10.11714/jsysu.med.YX20260030
- VernacularTitle:免疫检查点抑制剂耐药机制研究进展
- Author:
Caibo YANG
1
;
Liwu FU
1
Author Information
1. Sun Yat-sen University Cancer Center//State Key Laboratory of Oncology in South China//Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy//Department of Experimental Research， Guangdong Provincial Clinical Research Center for Cancer， Guangzhou 510060， China
- Publication Type:Review
- Keywords:
tumors;
immune checkpoint inhibitors;
drug resistance mechanisms;
tumor microenvironment;
combination therapy
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(4):613-626
- CountryChina
- Language:Chinese
-
Abstract:
Immune checkpoint inhibitors （ICIs） restore and enhance anti-tumor immune responses by relieving the suppressive regulatory mechanisms of the immune system， representing a landmark breakthrough in oncology that has fundamentally transformed the therapeutic paradigms for multiple malignancies and significantly prolonged survival in a subset of patients. However， clinical practice has revealed that the majority of patients develop primary resistance （initial non-response to therapy） or acquired resistance （resistance emerging after initial disease control） to ICIs treatment， substantially limiting their broad clinical application. The emergence of ICIs-resistant phenotypes may arise from diverse biological mechanisms， with complex and multifaceted resistance mechanisms encompassing alterations in tumor cell-intrinsic characteristics， tumor microenvironment （TME） remodeling， and host immune system status. In-depth investigation into ICIs resistance mechanisms and comprehensive understanding of these processes are essential for developing targeted resistance-overcoming strategies and improving the efficacy of cancer immunotherapy， which hold significant clinical implications and broad application prospects. This review provides a focused overview of ICIs resistance mechanisms with a summary of research advances in resistance-overcoming strategies. Resistance mechanisms include tumor cell-intrinsic factors， tumor microenvironmental factors， immune evasion-related mechanisms， and drug-related factors while resistance-overcoming strategies encompass combination therapies， novel target drug development， and tumor microenvironment modulation. With the understanding we aim to establish a theoretical foundation for enhancing ICIs therapeutic efficacy.
