Abstract 463: Differential cellular localization of programmed death ligand 1 (PD-L1) and enhanced expression of programmed death-1 (PD-1) in melanoma progression.

Abstract

Abstract Melanoma is an aggressive malignancy with a relatively high metastatic rate, responsible for almost 60% of lethal skin tumors. Although many human cancers such as melanoma express tumor antigens recognized by T cells, host immune responses often fail to control tumor growth for mostly unexplained reasons. Escaping immune destruction is one of the tenets of tumorigenesis; there have been several studies suggesting an important role of PD-1/PD-L1 (B7-H1) interactions in inhibiting the effector functions of cytotoxic T-lymphocyte in tumor. Ghebeh et al., reported that doxorubicin treatment caused decrease in cytosolic B7-H1 and increased nuclear translocalization in breast carcinoma (Breast Cancer Res. 2010;12(4):R48). It is unknown whether differential cellular expression of PD-L1 contributes to the pathogenesis of melanoma. To address the role of PD-L1 and its receptor PD-1 in different stages of malignant melanoma, we have performed semiquantitative immunohistochemical analysis of PD-L1 and PD-1 in benign nevi (n=59), primary melanomas without metastasis (n=22) or with metastasis (n=17), and melanoma metastases (n=32 cases). Benign nevi had significantly higher levels of nuclear PD-L1 immunopositivity (p=0.004) and low levels of PD-1 protein expression (p=0.002). With progression from benign nevi to primary melanoma there was an increase in cytoplasmic positivity for PD-L1 (p=0.03). Also, a significant positive correlation was observed between the percentage of positive cells (p=0.0007) and intensity (p=0.0009) for PD-1 in primary melanomas. Although there was no significant difference in PD-1 levels in between primaries with or without metastasis, a trend was observed for PD-L1 expression: primaries with metastasis having a larger number of tumor cells with cytosolic localization than primaries without metastasis (p=0.07). Interestingly, primary melanomas without metastasis showed significantly larger number of tumor infiltrating lymphocytes (TILs) cells having intense immunoreactivity for PD-L1 protein than did metastatic melanomas (p=0.03). In conclusion, differential cellular localization of PD-L1 protein and high levels of PD-1 protein correlates with disease progression and high-risk histologic features in melanoma and might partially explain the resistance of melanoma cells against the immune system. Citation Format: Nitin Chakravarti, Roland Bassett, Wen-Jen Hwu, Doina Ivan, Jonathan L. Curry, Victor G. Prieto. Differential cellular localization of programmed death ligand 1 (PD-L1) and enhanced expression of programmed death-1 (PD-1) in melanoma progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 463. doi:10.1158/1538-7445.AM2013-463