LIGHT, a novel ligand for lymphotoxin β receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer

Yifan Zhai, Ribo Guo, Tsui Ling Hsu, Guo Liang Yu, Jian Ni, Byoung S. Kwon, Gong Wei Jiang, Jiamo Lu, Jie Tan, Meena Ugustus, Kent Carter, Lorena Rojas, Feng Zhu, Clint Lincoln, Greg Endress, Lilly Xing, Sa Wang, Kwi O. Oh, Reiner Gentz, Steve RubenMarc E. Lippman, Shie Liang Hsieh, Dajun Yang

Research output: Contribution to journalArticle

225 Scopus citations

Abstract

LIGHT is a new member of tumor necrosis factor (TNF) cytokine family derived from an activated T cell cDNA library. LIGHT mRNA is highly expressed in splenocytes, activated PBL, CD8+ tumor infiltrating lymphocytes, granulocytes, and monocytes but not in the thymus and the tumor cells examined. Introduction of LIGHT cDNA into MDA-MB-231 human breast carcinoma caused complete tumor suppression in vivo. Histological examination showed marked neutrophil infiltration and necrosis in LIGHT expressing but not in the parental or the Neo-transfected MDA-MB-231 tumors. Interferon γ (IFNγ) dramatically enhances LIGHT-mediated apoptosis. LIGHT protein triggers apoptosis of various tumor cells expressing both lymphotoxin β receptor (LTβR) and TR2/HVEM receptors, and its cytotoxicity can be blocked specifically by addition of a LTβR-Fc or a TR2/HVEM-Fc fusion protein. However, LIGHT was not cytolytic to the tumor cells that express only the LTβR or the TR2/HVEM or hematopoietic cells examined that express only the TR2/HVEM, such as PBL, Jurkat cells, or CD8+ TIL cells. In contrast, treatment of the activated PBL with LIGHT resulted in release of IFNγ. Our data suggest that LIGHT triggers distinct biological responses based on the expression patterns of its receptors on the target cells. Thus, LIGHT may play a role in the immune modulation and have a potential value in cancer therapy.

Original languageEnglish (US)
Pages (from-to)1142-1151
Number of pages10
JournalJournal of Clinical Investigation
Volume102
Issue number6
DOIs
StatePublished - Sep 15 1998

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Keywords

  • Apoptosis
  • Breast cancer
  • LTβR
  • TNF
  • TR2/HVEM

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Zhai, Y., Guo, R., Hsu, T. L., Yu, G. L., Ni, J., Kwon, B. S., Jiang, G. W., Lu, J., Tan, J., Ugustus, M., Carter, K., Rojas, L., Zhu, F., Lincoln, C., Endress, G., Xing, L., Wang, S., Oh, K. O., Gentz, R., ... Yang, D. (1998). LIGHT, a novel ligand for lymphotoxin β receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer. Journal of Clinical Investigation, 102(6), 1142-1151. https://doi.org/10.1172/JCI3492