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Valliammai Muthappan, Janis M. Taube, Haiying Xu, Charles Eberhart, James T. Handa; Characterization of B7-H1 (PD-L1) and PD-1 Expression and Associated Inflammatory Infiltrates In Ocular Melanomas: Insight Into Immune Evasion. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5473.
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Aberrant B7-H1 (PD-L1) expression in the tumor microenvironment is associated with downregulation of native anti-tumor T-lymphocytes through the PD-1 receptor in non-ocular cancers, including cutaneous melanoma. Blocking antibodies against B7-H1 and PD-1 are currently under investigation in clinical trials, with the aim of restoring native immune surveillance in advanced disease. Preliminary results suggest that tumor expression of B7-H1 predicts response to these drugs. The expression of B7-H1 in ocular cancers is not yet known. In this study, we assess the presence and pattern of B7-H1 and PD-1 expression and associated inflammatory infiltrates in uveal melanomas.
A subset of eyes enucleated for melanoma at the Wilmer Eye Institute in the last 10 years was reviewed for the presence of inflammatory infiltrates and tissue availability. These cases were evaluated for B7-H1 expression by tumor (>5% membranous expression was considered positive), the presence of CD3+ tumor infiltrating T-lymphocytes (TILs), and PD-1 expression by TILs.
Eleven cases were identified. Tumor B7-H1 expression was seen in eight (72.7%), and PD-1 was expressed by TILs in nine tumors (81.8%). Eight cases (72.7%) were positive for all three markers and showed an interface pattern of B7-H1 positive tumor cells adjacent to PD-1 positive TILs. Of the three tumors (36.4%) in which B7-H1 was not expressed, there was only focal infiltration of TILs, mostly in the perivascular space. Of the two tumors that were PD-1 negative, both were of cases with rare TILs.
B7-H1 expression was observed in uveal melanomas, and topographically correlated with TILs, many of which expressed PD-1. The observed geographic patterns parallel those seen in cutaneous melanomas, and support the hypothesis that B7-H1 expression is not constitutive, but induced during the anti-tumor immune response. These results offer insight into adaptive immune evasion mechanisms by ocular melanomas, and also open the possibility of immunomodulatory therapy for cancers expressing B7-H1, either locally for primary tumors or systemically for metastatic tumors, to add to the currently limited treatment options for uveal melanoma patients.
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