Molecular pathways: next-generation immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1

Clin Cancer Res. 2012 Dec 15;18(24):6580-7. doi: 10.1158/1078-0432.CCR-12-1362. Epub 2012 Oct 19.


The aim of T-cell-based immune therapy for cancer has been to generate durable clinical benefit for patients. Following a generation of therapies that largely showed minimal activity, substantial toxicity, and no biomarkers to identify which patients benefit from treatment, early studies are showing signs that programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) inhibitors are highly active. Preclinical and early data from clinical studies suggest that targeting this pathway can induce durable clinical responses in patients in a variety of tumor types, including lung and colon cancer. Furthermore, correlations with tumor PD-L1 expression may enable selection of patients most likely to benefit from treatment. The emerging data not only offer the hope of better cancer therapy but also provide evidence that changes our understanding of how the host immune system interacts with human cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / metabolism
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Immunotherapy
  • Molecular Targeted Therapy
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism


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