PD-L1 and Emerging Biomarkers in Immune Checkpoint Blockade Therapy

Cancer J. 2018 Jan/Feb;24(1):41-46. doi: 10.1097/PPO.0000000000000301.


PD-L1 checkpoint blockade is revolutionizing cancer therapy, and biomarkers capable of predicting which patients are most likely to respond are highly desired. The detection of PD-L1 protein expression by immunohistochemistry can enrich for response to anti-PD-(L)1 blockade in a variety of tumor types, but is not absolute. Limitations of current commercial PD-L1 immunohistochemical (IHC) assays and improvements anticipated in next-generation PD-L1 testing are reviewed. Assessment of tumor-infiltrating lymphocytes in conjunction with PD-L1 testing could improve specificity by distinguishing adaptive (interferon γ driven and cytotoxic T-lymphocyte associated) from constitutive (non-immune mediated) expression. The presence of a high tumor mutational burden also enriches for response to therapy, and early data indicate that this may provide additive predictive value beyond PD-L1 IHC alone. As candidate biomarkers continue to emerge, the pathologist's assessment of the tumor microenvironment on hematoxylin-eosin stain combined with PD-L1 IHC remains a rapid and robust way to evaluate the tumor-immune dynamic.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / metabolism*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Mutation / drug effects
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism*
  • Tumor Burden / drug effects
  • Tumor Microenvironment / drug effects


  • Biomarkers, Tumor
  • Programmed Cell Death 1 Receptor