Biomarkers for Immune Checkpoint Inhibitor Response in NSCLC: Current Developments and Applicability

Int J Mol Sci. 2023 Jul 25;24(15):11887. doi: 10.3390/ijms241511887.

Abstract

Lung cancer has the highest mortality rate among all cancer types, resulting in over 1.8 million deaths annually. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of non-small cell lung cancer (NSCLC). ICIs, predominantly monoclonal antibodies, modulate co-stimulatory and co-inhibitory signals crucial for maintaining immune tolerance. Despite significant therapeutic advancements in NSCLC, patients still face challenges such as disease progression, recurrence, and high mortality rates. Therefore, there is a need for predictive biomarkers that can guide lung cancer treatment strategies. Currently, programmed death-ligand 1 (PD-L1) expression is the only established biomarker for predicting ICI response. However, its accuracy and robustness are not consistently reliable. This review provides an overview of potential biomarkers currently under development or in the validation stage that hold promise in improving the classification of responders and non-responders to ICI therapy in the near future.

Keywords: PD-L1; immune checkpoint inhibitors; immunotherapy; non-small cell lung cancer; predictive biomarkers.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen
  • Biomarkers
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods
  • Lung Neoplasms* / metabolism
  • Programmed Cell Death 1 Receptor

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • Biomarkers
  • B7-H1 Antigen
  • Biomarkers, Tumor

Grants and funding

This research was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil, grant number 2019/07111-9 and by institutional funding of Barretos Cancer Hospital (Brazil). K.T. was a recipient of scholarship from FAPESP (2021/08352-0). A.P.S. was a recipient of scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil. L.M.R.B.A. was a recipient of a scholarship from FAPESP (2021/04100-6). L.M.R.B.A., L.F.L. and R.M.R. are a recipient of a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Productivity (Brazil) fellowship.