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Clin Cancer Res. 2015 Jul 1;21(13):3052-60. doi: 10.1158/1078-0432.CCR-14-3073. Epub 2015 Mar 18.

Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites.

Author information

1
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut. harriet.kluger@yale.edu.
2
Department of Biology, School of Health and Natural Sciences, University of Saint Joseph, West Hartford, Connecticut.
3
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
4
Department of Neurosurgery and Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
5
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
6
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut.

Abstract

PURPOSE:

Programmed death ligand-1 (PD-L1) tumor expression represents a mechanism of immune escape for melanoma cells. Drugs blocking PD-L1 or its receptor have shown unprecedented activity in melanoma, and our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in metastatic melanomas.

EXPERIMENTAL DESIGN:

We used a tissue microarray (TMA) consisting of two cores from 95 metastatic melanomas characterized for clinical stage, outcome, and anatomic site of disease. We assessed PD-L1 expression and tumor-infiltrating lymphocyte (TIL) content (total T cells and CD4/CD8 subsets) by quantitative immunofluorescence.

RESULTS:

High PD-L1 expression was associated with improved survival (P = 0.02) and higher T-cell content (P = 0.0005). Higher T-cell content (total and CD8 cells) was independently associated with improved overall survival; PD-L1 expression was not independently prognostic. High TIL content in extracerebral metastases was associated with increased time to developing brain metastases (P = 0.03). Cerebral and dermal metastases had slightly lower PD-L1 expression than other sites, not statistically significant. Cerebral metastases had less T cells (P = 0.01).

CONCLUSIONS:

T-cell-infiltrated melanomas, particularly those with high CD8 T-cell content, are more likely to be associated with PD-L1 expression in tumor cells, an improved prognosis, and increased time to development of brain metastases. Studies of T-cell content and subsets should be incorporated into trials of PD-1/PD-L1 inhibitors to determine their predictive value. Furthermore, additional studies of anatomic sites with less PD-L1 expression and T-cell infiltrate are needed to determine if discordant responses to PD-1/PD-L1 inhibitors are seen at those sites.

PMID:
25788491
PMCID:
PMC4490112
DOI:
10.1158/1078-0432.CCR-14-3073
[Indexed for MEDLINE]
Free PMC Article

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