Constitutive expression and costimulatory function of LIGHT/TNFSF14 on human melanoma cells and melanoma-derived microvesicles

Roberta Mortarini, Alessia Scarito, Daisuke Nonaka, Marina Zanon, Ilaria Bersani, Elisabetta Montaldi, Elisabetta Pennacchioli, Roberto Patuzzo, Mario Santinami, Andrea Anichini

Research output: Contribution to journalArticlepeer-review

Abstract

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 β 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 β 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.

Original languageEnglish
Pages (from-to)3428-3436
Number of pages9
JournalCancer Research
Volume65
Issue number8
Publication statusPublished - Apr 15 2005

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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