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 Ruben & 3 others Marc E Lippman, Shie Liang Hsieh, Dajun Yang

Research output: Contribution to journalArticle

222 Citations (Scopus)

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
Pages (from-to)1142-1151
Number of pages10
JournalJournal of Clinical Investigation
Volume102
Issue number6
StatePublished - Sep 15 1998
Externally publishedYes

Fingerprint

Lymphotoxin-alpha
Apoptosis
Ligands
Light
Genes
Neoplasms
Tumor Necrosis Factor Ligand Superfamily Member 14
Interferons
Thymus Neoplasms
Tumor-Infiltrating Lymphocytes
Jurkat Cells
Fc Receptors
Neutrophil Infiltration
Gene Library
Granulocytes
Monocytes
Necrosis
Complementary DNA
Tumor Necrosis Factor-alpha
Breast Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

LIGHT, a novel ligand for lymphotoxin β receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer. / Zhai, Yifan; Guo, Ribo; Hsu, Tsui Ling; Yu, Guo Liang; Ni, Jian; Kwon, Byoung S.; Jiang, Gong Wei; Lu, Jiamo; Tan, Jie; Ugustus, Meena; Carter, Kent; Rojas, Lorena; Zhu, Feng; Lincoln, Clint; Endress, Greg; Xing, Lilly; Wang, Sa; Oh, Kwi O.; Gentz, Reiner; Ruben, Steve; Lippman, Marc E; Hsieh, Shie Liang; Yang, Dajun.

In: Journal of Clinical Investigation, Vol. 102, No. 6, 15.09.1998, p. 1142-1151.

Research output: Contribution to journalArticle

Zhai, Y, Guo, R, Hsu, TL, Yu, GL, Ni, J, Kwon, BS, Jiang, GW, Lu, J, Tan, J, Ugustus, M, Carter, K, Rojas, L, Zhu, F, Lincoln, C, Endress, G, Xing, L, Wang, S, Oh, KO, Gentz, R, Ruben, S, Lippman, ME, Hsieh, SL & 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, vol. 102, no. 6, pp. 1142-1151.
Zhai, Yifan ; Guo, Ribo ; Hsu, Tsui Ling ; Yu, Guo Liang ; Ni, Jian ; Kwon, Byoung S. ; Jiang, Gong Wei ; Lu, Jiamo ; Tan, Jie ; Ugustus, Meena ; Carter, Kent ; Rojas, Lorena ; Zhu, Feng ; Lincoln, Clint ; Endress, Greg ; Xing, Lilly ; Wang, Sa ; Oh, Kwi O. ; Gentz, Reiner ; Ruben, Steve ; Lippman, Marc E ; Hsieh, Shie Liang ; Yang, Dajun. / LIGHT, a novel ligand for lymphotoxin β receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer. In: Journal of Clinical Investigation. 1998 ; Vol. 102, No. 6. pp. 1142-1151.
@article{3772bdcf5a344b4c8440a31ea91710a3,
title = "LIGHT, a novel ligand for lymphotoxin β receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer",
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.",
keywords = "Apoptosis, Breast cancer, LTβR, TNF, TR2/HVEM",
author = "Yifan Zhai and Ribo Guo and Hsu, {Tsui Ling} and Yu, {Guo Liang} and Jian Ni and Kwon, {Byoung S.} and Jiang, {Gong Wei} and Jiamo Lu and Jie Tan and Meena Ugustus and Kent Carter and Lorena Rojas and Feng Zhu and Clint Lincoln and Greg Endress and Lilly Xing and Sa Wang and Oh, {Kwi O.} and Reiner Gentz and Steve Ruben and Lippman, {Marc E} and Hsieh, {Shie Liang} and Dajun Yang",
year = "1998",
month = "9",
day = "15",
language = "English",
volume = "102",
pages = "1142--1151",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - LIGHT, a novel ligand for lymphotoxin β receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer

AU - Zhai, Yifan

AU - Guo, Ribo

AU - Hsu, Tsui Ling

AU - Yu, Guo Liang

AU - Ni, Jian

AU - Kwon, Byoung S.

AU - Jiang, Gong Wei

AU - Lu, Jiamo

AU - Tan, Jie

AU - Ugustus, Meena

AU - Carter, Kent

AU - Rojas, Lorena

AU - Zhu, Feng

AU - Lincoln, Clint

AU - Endress, Greg

AU - Xing, Lilly

AU - Wang, Sa

AU - Oh, Kwi O.

AU - Gentz, Reiner

AU - Ruben, Steve

AU - Lippman, Marc E

AU - Hsieh, Shie Liang

AU - Yang, Dajun

PY - 1998/9/15

Y1 - 1998/9/15

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Breast cancer

KW - LTβR

KW - TNF

KW - TR2/HVEM

UR - http://www.scopus.com/inward/record.url?scp=0032530318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032530318&partnerID=8YFLogxK

M3 - Article

VL - 102

SP - 1142

EP - 1151

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -