Mechanisms and Clinical Applications of Tumor Mutational Burden in Non-Small Cell Lung Cancer

Abstract

Over the past few years, ICIs have rapidly emerged as primary standard treatments for advanced NSCLC, offering new therapeutic directions for the disease. However, some remain unresponsive to ICIs or develop resistance. Therefore, the development of predictive biomarkers is critically important for accurately identifying patients most likely to respond to immunotherapy. TMB serves as a promising biomarker in cancer immunotherapy, effectively assessing the tumor's neoantigen load. Tumor cells with high TMB can generate neoantigens, activating T cells to attack tumor cells and produce an immunotherapy response. Therefore, the presence of a high TMB in patients with NSCLC treated with ICIs correlates with sustained clinical responses and improved long-term outcomes. This paper elucidates the mechanism of action of TMB as a biomarker in immunotherapy for NSCLC, evaluates its clinical utility (demonstrating significantly improved ORR, PFS, and OS in patients with high TMB when combined with monoclonal antibodies) and identifies its limitations (including insufficient testing standardization and inability to directly reflect mutation burden). These findings aim to provide additional theoretical reference for clinical practice.