PD-L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti-PD-1/PD-L1 clinical trials

Pigment Cell Melanoma Res. 2015 May;28(3):245-53. doi: 10.1111/pcmr.12340. Epub 2014 Dec 22.


This study evaluated the expression of PD-L1 in immunotherapy-naïve metastatic melanoma patients to determine longitudinal intrapatient concordance and correlate PD-L1 status with clinicopathologic characteristics and outcome. PD-L1 expression was assessed by immunohistochemistry in 58 patients (43 primary tumors, 96 metastases). Seventy-two percent of patients had at least one specimen expressing PD-L1 in ≥ 1% of tumor cells. Median positive tumor cell count overall was low (8% in nonzero specimens). PD-L1 expression was frequently discordant between primary tumors and metastases and between intrapatient metastases, such that 23/46 longitudinal patient specimens were discordant. PD-L1 was associated with higher TIL grade but not with other known prognostic features. There was a positive univariate association between PD-L1 expression in locoregional metastases and melanoma-specific survival, but the effect was not observed for primary melanoma. In locoregional lymph node metastasis, PD-L1+/TIL+ patients had the best outcome, and PD-L1+/TIL- patients had poor outcome.

Keywords: PD-1; PD-L1; biomarker; diagnosis; heterogeneity; immunotherapy; melanoma; metastasis; pathology; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / metabolism*
  • Clinical Trials as Topic*
  • Female
  • Genetic Heterogeneity
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Melanoma / immunology
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Prognosis
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Survival Analysis


  • B7-H1 Antigen