LAG-3 and TIGIT protein expressions in cutaneous melanoma and their relationship with PD-1 tumor-infiltrating lymphocytes

Abstract Background Lymphocyte activating gene 3 (LAG-3) and T cell immunoglobulin and ITIM domain (TIGIT) are emerging checkpoint proteins. Objective We evaluated LAG-3 and TIGIT protein expression patterns and correlation with programmed death-1 (PD-1) expression, and determined their effects on clinicopathological characteristics and biological responses in melanoma. Methods Diagnostic tissue from 124 cases of melanoma was evaluated by immunohistochemistry for LAG-3, TIGIT, and PD-1 expression. Clinicopathological features and survivals were analyzed according to the expression of LAG-3, TIGIT, and PD-1. Results LAG-3 and TIGIT expression on tumor infiltrating lymphocytes was significantly correlated with that of PD-1 expression, and was also significantly associated with negative prognostic factors: deeper Breslow thickness, lymph node involvement, and advanced stage of disease. However, PD-1 expression was not associated with clinicopathological variables, which are a prognostic index. High expression of either LAG-3 or TIGIT was associated with worse survivals. Subgroup analysis on the basis of Breslow thickness showed that both LAG-3 and TIGIT have prognostic significance regardless of tumor thickness. High expression of PD-1 was not predictive for survivals. Limitations Retrospective study in a single institution and possibility of type 1 error. Conclusion Expression of LAG-3 and TIGIT represents an independent unfavorable prognostic factor in cutaneous melanoma.