Predictive biomarkers of response for immune checkpoint inhibitors in non-small-cell lung cancer

Eur J Cancer. 2019 Jan;106:144-159. doi: 10.1016/j.ejca.2018.11.002. Epub 2018 Dec 5.


Immune checkpoint blockade has been a pivotal development in the management of advanced non-small-cell lung cancer (NSCLC). Although durable antitumour activity and improved survival have been observed in a subset of patients, there is a need for additional predictive biomarkers to improve patient selection and avoid toxicity in potential non-responders. This review will address the use and limitations of tumour programmed death-ligand 1 expression as a predictive biomarker and review emerging biomarker strategies specifically related to NSCLC including genetic alterations (tumour mutation burden, loss and gain activated mutations), tumour-related factors (tumour microenvironment) and factors related to the host immune system. Novel approaches in biomarker detection such as peripheral blood monitoring will also be reviewed.

Keywords: Immunotherapy; Lung cancer; Microsatellite instability; NSCLC; PD-L1; Predictive biomarkers; Tumour microenvironment; Tumour mutational burden.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / immunology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Mutation
  • Predictive Value of Tests
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Risk Assessment
  • Risk Factors
  • Signal Transduction
  • Transcriptome
  • Treatment Outcome
  • Tumor Microenvironment


  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor