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

Front Immunol. 2025 May 8:16:1554871. doi: 10.3389/fimmu.2025.1554871. eCollection 2025.

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.

Keywords: NSCLC; biomarker; circulating biomarkers; immune checkpoint inhibitors; tertiary lymphoid structures.

Publication types

  • Review

MeSH terms

  • Animals
  • B7-H1 Antigen
  • Biomarkers, Tumor* / genetics
  • Carcinoma, Non-Small-Cell Lung* / diagnosis
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / immunology
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / therapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Prognosis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • B7-H1 Antigen