PD-L1, PD-L2 and PD-1 expression in metastatic melanoma: Correlation with tumor-infiltrating immune cells and clinical outcome

Joseph M. Obeid, Gulsun Erdag, Mark E. Smolkin, Donna H. Deacon, James W. Patterson, Leiping Chen, Timothy N. Bullock, Craig L. Slingluff

Research output: Contribution to journalArticlepeer-review

Abstract

Therapeutic blockade of PD-1/PD-L1 can have dramatic therapeutic benefit in some patients; however, the prognostic associations of PD-1 and its ligands, in the absence of therapeutic blockade have not been definitively addressed. In particular, associations of PD-L2 with immune infiltrates and with outcome have yet to be explored. We hypothesized that surface expression of both PD-L1 and PD-L2 by melanoma cells would be associated with immune cell infiltration and with overall patient survival, independent of checkpoint blockade therapy. We also characterized the heterogeneity of their distribution within a tumor and within tumors of the same patient. Tissue microarrays of metastatic melanoma samples from 147 patients were quantified for CD8+, CD45, CD4+, CD3, CD163, CD20, CD138, FoxP3, PD-1, PD-L1 and PD-L2 markers by immunohistochemistry. Relationships between the proportions of PD-L1 and PD-L2 expressing tumor cells with the immune cell count, distribution (immunotype) and patient survival were studied. Expressions of both PD-L1 and PD-L2 correlated significantly with increasing densities of immune cells in the tumor specimens and with immunotype. Positive PD-L2 expression was associated with improved overall survival and the simultaneous positive expression of both PD-1 ligands showed a higher association with survival. Significant heterogeneity of PD-L1 and PD-L2 expressions within tumors were observed, however, they were less pronounced with PD-L2. In conclusion, both are markers of immune infiltration and PD-L2, alone or in combination with PD-L1, is a marker for prognosis in metastatic melanoma patients. Larger tumor samples yield more reliable assessments of PD-L1/L2 expression.

Original languageEnglish (US)
Article numbere1235107
JournalOncoImmunology
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2016

Keywords

  • Immune checkpoint
  • PD-1
  • PD-L1
  • PD-L2
  • immune infiltrates
  • metastatic melanoma
  • patient outcomes
  • tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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