[Immunotherapy in non-small cell lung cancer: inhibition of PD1/PDL1 pathway]

Rev Pneumol Clin. 2015 Feb;71(1):44-56. doi: 10.1016/j.pneumo.2014.11.004. Epub 2015 Feb 14.
[Article in French]

Abstract

Despite recent advances in targeted therapy of non-small cell lung cancer (NSCLC), many patients do not benefit from these therapies. Inhibition of PD1/PDL1 is an interesting therapeutic target which restores the immune system against tumor cells. PD1 is located on lymphocytes and PDL1 on the antigen presenting cells. PD1 and PDL1 are co-inhibition molecules and their interaction results in immune tolerance against tumor cells. Anti-PD1 and anti-PDL1 antibodies have been developed to restore immune system in solid cancer including NSCLC. In phase I, studies assessing nivolumab, an anti-PD1 antibody, objective responses were observed in 13 to 18% of NSCLC patients failing previous treatment. The data obtained with anti-PDL1 antibodies is similar with objective responses ranging from 6 to 22%. The encouraging results of phase I/II studies must be confirmed in ongoing phase III studies. Anti-PD1 and anti-PDL1 antibodies exposed to new adverse events including auto-immune diseases whose support is not codified. Questions about treatment duration and criteria evaluation are not resolved. These treatments pave the way for immunomodulation in NSCLC treatment.

Keywords: Cancer bronchique non à petites cellules; Immunotherapie; Immunotherapy; Non-small cell lung cancer; Programmed death 1; Programmed death ligand 1.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Humans
  • Immunotherapy / methods*
  • Lung Neoplasms / therapy*
  • Nivolumab
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Signal Transduction / drug effects

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab