Jin Zhaoyang

Shandong University of Traditional Chinese Medicine

Abstract：

Immune checkpoint inhibitors (ICIs) block the negative regulatory effects of immune checkpoint molecules to reactivate host anti-tumor immune responses, representing a revolutionary breakthrough in solid tumor therapy and significantly improving prognoses for patients with common solid tumors such as lung cancer, gastric cancer, and melanoma. However, clinical practice reveals varying degrees of resistance to ICI therapy in most solid tumor patients, including primary resistance (no initial response) and acquired resistance (disease progression after initial response), severely limiting the clinical utility of ICIs. This review systematically outlines the core mechanisms of ICIs in solid tumors, defines the major resistance subtypes and their clinical characteristics, and provides an in-depth analysis of key resistance mechanisms mediated by tumor cell-intrinsic factors, the tumor microenvironment, host factors, and other relevant components. It also summarizes currently used detection technologies for resistance, risk assessment systems, and their respective advantages and limitations. Finally, the current state of research in this field is summarized and future perspectives are discussed, providing a theoretical basis and research directions for developing strategies to reverse ICI resistance, optimize immunotherapy regimens for solid tumors, and enhance patient therapeutic benefits.

Key Words：

immune checkpoint inhibitors; solid tumors; resistance mechanisms; tumor microenvironment; primary resistance; acquired resistance