Anti-PD-1 therapy in melanoma

Semin Oncol. 2015 Jun;42(3):466-73. doi: 10.1053/j.seminoncol.2015.02.008. Epub 2015 Feb 13.


Immune-regulatory mechanisms are used by cancer to hide from the immune system. Advances and in-depth understanding of the biology of melanoma and its interaction with the immune system have led to the development of some of antagonistic antibodies to the programmed death 1 pathway (PD-1) and one of its ligands, programmed death ligand 1 (PD-L1), which are demonstrating high clinical benefit rates and tolerability. Blocking the immune-regulatory checkpoints that limit T-cell responses to melanoma upon PD-1/PD-L1 modulation has provided clinically validated targets for cancer immunotherapy. Combinations with other anti-melanoma agents may result in additional benefits. Nivolumab, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers. Long-term survivors already have been reported with these therapies. In this review, we discuss the current state of anti-PD-1 agents, the evidence in the literature to support the combination of anti-PD-1 antibodies with other anti-cancer agents and discuss the future directions for rational design of clinical trials that keep on increasing the number of long-term survivors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Immunotherapy
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / metabolism
  • Molecular Targeted Therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism


  • Antineoplastic Agents
  • Immunologic Factors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor