The role of antagonists of the PD-1:PD-L1/PD-L2 axis in head and neck cancer treatment

Oral Oncol. 2016 Oct;61:152-8. doi: 10.1016/j.oraloncology.2016.08.001. Epub 2016 Aug 5.


We review the current clinical knowledge surrounding one of the most promising immune checkpoint pathways currently investigated in head and neck squamous cell carcinoma patients, programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2). We review ongoing clinical trials and associated clinical responses observed with targeting the receptor, PD-1, and its ligand, PD-L1. A recent phase III clinical trial (Checkmate 141) demonstrated an improved overall survival in head and neck cancer patients treated with anti-PD-1 monotherapy as compared to standard of care for recurrent and/or metastatic disease, which raises questions on how best to incorporate immunotherapy in the context of standard of care. We discuss biomarkers of response to this class of novel drugs, which is an area of active investigation. Lastly, we project future directions in the field wherein understanding how the Fc portions of the various monoclonal antibodies may impact their clinical efficacy as well as discuss areas where our next advances may take place, such as combination strategies.

Keywords: B7-H1; Head and neck cancer; Immune checkpoint; Immunotherapy; PD-1; PD-L1; PD-L2; Squamous cell carcinoma.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors*
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Programmed Cell Death 1 Ligand 2 Protein / antagonists & inhibitors*
  • Tumor Microenvironment


  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein