Oncotarget

Research Papers:

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 and Martine J. Jager _

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Oncotarget. 2017; 8:54722-54734. https://doi.org/10.18632/oncotarget.18039

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Abstract

Jinfeng Cao1,2,*, Niels J. Brouwer1,*, Kate E. Richards1, Marina Marinkovic1, Sjoerd van Duinen3, Daan Hurkmans1, Els M.E. Verdegaal5, Ekaterina S. Jordanova3,4,# and Martine J. Jager1,#

1Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands

2Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China

3Department of Obstetrics and Gynaecology, Center for Gynaecological Oncology Amsterdam (CGOA), VU University Medical Center, Amsterdam, The Netherlands

4Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

5Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands

*These authors contributed equally to this work

#These authors shared senior authorship

Correspondence to:

Martine J. Jager, email: [email protected]

Keywords: conjunctival melanoma, PD-L1, PD-1, CTL, immunotherapy

Received: February 25, 2017     Accepted: May 08, 2017     Published: May 20, 2017

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 vitro results 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.


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