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

Area of Science:

• Oncology
• Immunology
• Ophthalmology

Background:

• Conjunctival melanoma (CM) is a rare but aggressive cancer with limited treatment options for metastatic disease.
• Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis have shown efficacy in various cancers.

Purpose of the Study:

• To investigate the expression of PD-1 and PD-L1 in primary conjunctival melanoma.
• To assess the correlation between PD-1/PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and clinical outcomes.
• To evaluate the therapeutic potential of targeting the PD-1/PD-L1 axis in CM.

Main Methods:

• Immunofluorescence staining of PD-1 and PD-L1 on 27 primary CM samples.
• Analysis of TIL density and correlation with clinical parameters.
• Flow cytometry to assess PD-1/PD-L1 expression in conjunctival and cutaneous melanoma cell lines.
• In vitro interferon gamma stimulation assays.

Main Results:

• PD-L1 was expressed on tumor cells in 19% of CM cases and on stromal cells (M2 macrophages) in 59% of cases.
• Tumoral PD-L1 expression was linked to distant metastases and reduced melanoma-specific survival.
• PD-1 expression was observed in 63% of T2 stage tumors.
• TIL density was higher in smaller tumors but not correlated with survival or PD-1/PD-L1 expression.
• Melanoma cell lines showed inducible PD-L1 expression upon interferon gamma stimulation.

Conclusions:

• The PD-1/PD-L1 axis is expressed in conjunctival melanoma, with tumoral PD-L1 associated with adverse outcomes.
• PD-1/PD-L1 pathway inhibition represents a potential therapeutic strategy for CM.
• Further clinical evaluation of PD-1/PD-L1 blockade in CM is warranted.