免疫检查点抑制剂耐药机制研究进展OA

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.