Novel immunotherapeutic approaches in lung cancer: driving beyond programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte-associated Protein-4

Curr Opin Oncol. 2025 Jan 1;37(1):48-62. doi: 10.1097/CCO.0000000000001106. Epub 2024 Oct 28.

Abstract

Purpose of review: In this review, our aim is to highlight the latest novel immunotherapeutic approaches for advanced nonsmall cell lung cancer (NSCLC) beyond anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) and anti- cytotoxic T-lymphocyte-associated Protein-4 (CTLA4).

Recent findings: Immune checkpoint inhibitors (ICIs) revolutionized the treatment of advanced NSCLC. Despite that, patients develop primary or acquired resistance to ICIs. The discovery of novel approaches represents both an unmet need and an opportunity to improve outcomes in these patients.

Summary: We summarized the most relevant novel immune checkpoints, many of them in their early phase of testing, to provide a comprehensive overview of the state of the art of immunotherapy in NSCLC beyond PD-1/PD-L1 and CTL-4 inhibitors.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • CTLA-4 Antigen* / antagonists & inhibitors
  • CTLA-4 Antigen* / immunology
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / immunology
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology

Substances

  • Immune Checkpoint Inhibitors
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor
  • B7-H1 Antigen
  • CTLA4 protein, human
  • CD274 protein, human
  • PDCD1 protein, human