Density of high endothelial venules and PDL-1 expression: relationship with tumor-infiltrating lymphocytes in primary cutaneous melanomas

Abstract

Abstract Studies have highlighted melanoma immunogenicity, and the prognostic importance of tumor infiltrating lymphocytes (TILs) and mechanisms of tumor immune evasion, such as hyperexpression of programmed cell death ligand 1 (PDL-1). High endothelial venules (HEV) are specialized blood vessels that can facilitate the lymphocytes migration to the tumor. Here we evaluate the association of HEV density and PDL-1 expression in primary cutaneous melanomas with the presence and degree of TILs and with other clinicopathological variables (age, sex, tumor location, melanoma histological type, Breslow thickness, ulceration, regression signs, mitotic index). HEV density and PDL-1 expression were assessed immunohistochemically in 78 melanoma cases, using a specific antibody, and were detected in 59% and 76% of these, respectively. Positive associations were identified between HEV density and PDL-1 expression with the presence and degree of lymphocytic infiltration, melanoma histological type and ulceration presence. No correlation was found between HEV density and PDL-1 expression. Our findings confirm the HEV role in the recruitment and facilitation of lymphocyte transport in cutaneous melanomas, where HEV density is strongly associated with the degree of TILs. Additionally, PDL-1 hyperexpression suggests a possible mechanism of tumor immune evasion, which may lead to inactivation and reduction of the tumor lymphocytes number.

Keywords

• MECA-79
• Melanoma
• PDL-1M
• tumor infiltrating lymphocytes
• tumor microenvironment