Constitutive Expression and Costimulatory Function of LIGHT/TNFSF14 on Human Melanoma Cells and Melanoma-Derived Microvesicles

Neoplastic cells are thought to have defective expression of costimulatory molecules. However, in this study, we show that human melanoma cells express LIGHT//TNFSF14, a ligand of herpesvirus entry mediator on T cells and of lymphotoxin B receptor on stromal cells. In vitro, melanoma cells stained for LIGHT in the intracellular compartment, with weak or negative cell surface expression. However, LIGHT was expressed on tumor-derived microvesicles released from melanoma cells. In vivo, LIGHT was found in metastatic lesions, and the extent of lymphotoxin B receptor expression on the stromal cells was significantly associated with a‘‘brisk’’ T-cell infiltrate in the neoplastic tissue. In the lesions with a brisk T-cell infiltrate, stromal cells surrounding the tumor also stained for the T-cell attractant chemokine CCL21. The intratumoral T lymphocytes frequently expressed herpesvirus entry mediator and were characterized by a differentiated phenotype. Coculture of lymphocytes with LIGHT + melanomaderived microvesicles or even with LIGHT + melanoma cells in the presence of interleukin-2 costimulated LIGHT-dependent CD3 + CD8 + T-cell proliferation. However, lymphocyte coculture with LIGHT + microvesicles in the presence of interleukin-2 was also associated with an apoptotic response as documented by increased binding of Annexin V by CD3 + CD8 + Tcells. These data suggest that LIGHTconstitutively expressed in human melanoma cells and microvesicles may contribute to regulate T-cell responses to tumor cells. (Cancer Res 2005; 65(8): 3428-36)