PD-L1/PD-1 expression and tumor-infiltrating lymphocytes in conjunctival melanoma

Jinfeng Cao, Niels J Brouwer, Kate E Richards, Marina Marinkovic, Sjoerd van Duinen, Daan Hurkmans, Els M E Verdegaal, Ekaterina S Jordanova, Martine J Jager

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Conjunctival melanoma (CM) is an infrequent but potentially lethal malignancy, with limited therapeutic options for metastases. Recent inhibitors of the interaction of programmed cell death protein 1 (PD-1) and its ligand PD-L1 are associated with good clinical responses in many malignancies. To investigate the therapeutic potential of targeting the PD-1/PD-L1 axis in CM, we analyzed the expression of PD-1 and PD-L1 and the density of various types of tumor-infiltrating lymphocytes (TILs) in primary CM (n= 27), using immunofluorescence staining. Results were compared with clinical parameters and outcome. Flow cytometry was exploited to determine the PD-L1 and PD-1 protein expression in conjunctival and cutaneous melanoma cell lines. PD-L1 expression was identified on tumor cells in five (19%) primary CM and on stromal cells (mainly CD68+CD163+M2 macrophages) in 16 (59%) cases. PD-L1 expression on tumor cells was associated with the presence of distant metastases and a worse melanoma-related survival. PD-1 expression was seen in 17 (63%) cases, all of which were T2 stage tumors. Small tumors had a higher density of TILs than large tumors. The density of TILs was not correlated with survival, tumoral/stromal PD-L1 or PD-1 expression.In vitroresults showed that most CM and cutaneous melanoma cell lines do not constitutively express PD-L1. However, expression could be upregulated after interferon gamma stimulation. Our findings suggest that blocking the PD-1/PD-L1 axis should be evaluated as a treatment for CM.

Original languageEnglish
Pages (from-to)54722-54734
Number of pages13
JournalOncotarget
Volume8
Issue number33
DOIs
Publication statusPublished - 15 Aug 2017

Cite this

Cao, J., Brouwer, N. J., Richards, K. E., Marinkovic, M., van Duinen, S., Hurkmans, D., ... Jager, M. J. (2017). PD-L1/PD-1 expression and tumor-infiltrating lymphocytes in conjunctival melanoma. Oncotarget, 8(33), 54722-54734. https://doi.org/10.18632/oncotarget.18039