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 beta 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 beta 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(+)
melanoma-derived 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(+) T cells. These data suggest that LIGHT constitutively expressed in human
melanoma cells and microvesicles may contribute to regulate T-cell responses to
tumor cells.