AUTHOR=Zhang Jiacheng , Song Zehao , Zhang Yuanjie , Zhang Chentong , Xue Qi , Zhang Guochao , Tan Fengwei 

TITLE=Recent advances in biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1554871

DOI=10.3389/fimmu.2025.1554871

ISSN=1664-3224

ABSTRACT=Lung cancer continues to be the primary cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all instances. Recently, immune checkpoint inhibitors (ICIs) have transformed the treatment approach for NSCLC, however, only a subset of patients experiences significant benefits. Therefore, identifying reliable biomarkers to forecast the efficacy of ICIs is crucial for ensuring the safety and effectiveness of treatments, becoming a major focus of current research efforts. This review highlights the recent advances in predictive biomarkers for the efficacy of ICIs in the treatment of NSCLC, including PD-L1 expression, tertiary lymphoid structures (TLS), tumor-infiltrating lymphocytes (TILs), tumor genomic alterations, transcriptional signatures, circulating biomarkers, and the microbiome. Furthermore, it underscores the pivotal roles of liquid biopsy, sequencing technologies, and digital pathology in biomarker discovery. Special attention is given to the predictive value of TLS, circulating biomarkers, and transcriptional signatures. The review concludes that the integration of multiple biomarkers holds promise for achieving more accurate efficacy predictions and optimizing personalized immunotherapy strategies. By providing a comprehensive overview of the current progress, this review offers valuable insights into biomarker-based precision medicine for NSCLC and outlines future research directions.