TY - JOUR
T1 - A role for HVEM, but not lymphotoxin-beta receptor, in LIGHT-induced tumor cell death and chemokine production
AU - Pasero, Christine
AU - Barbarat, Bernadette
AU - Just-Landi, Sylvaine
AU - Bernard, Alain
AU - Aurran-Schleinitz, Thérèse
AU - Rey, Jérome
AU - Eldering, Eric
AU - Truneh, Alemsedeg
AU - Costello, Régis T.
AU - Olive, Daniel
PY - 2009
Y1 - 2009
N2 - The TNF member LIGHT also known as TL4 or TNFSF14) can play a major role in cancer control via its two receptors; it induces tumor cell death through lymphotoxin-P receptor (LT-beta R) and ligation to the herpes virus entry mediator (HVEM) amplifies the immune response. By studying the effect of LIGHT in the transcriptional profile of a lymphoid malignancy, we found that HVEM, but not LT-beta R, stimulation induces a significant increase in the expression of chemokine genes such as IL-8, and an unexpected upregulation of apoptotic genes. This had functional consequences, since LIGHT, or HVEM mAb, thus far known to costimulate T- and B-cell activation, induced chronic lymphocytic leukemia cell death. Many of the mediators involved were identified here, with an apoptotic pathway as demonstrated by caspases activation, decrease in mitochondrial membrane potential, upregulation of the pro-apoptotic protein Bax, but also a role of TRAIL. Moreover, HVEM induced endogenous TNF-alpha production and TNF-alpha enhanced HVEM-mediated cell death. HVEM function was mainly dependent on LIGHT, since other ligands like HSV-glycoprotein D and B and T lymphocyte attenuator were essentially ineffective. in conclusion, we describe a novel, as yet unknown killing effect of LIGHT through HVEM on a lymphoid malignancy, and combined with induction of chemokine release this may represent an additional tool to boost cancer immunotherapy
AB - The TNF member LIGHT also known as TL4 or TNFSF14) can play a major role in cancer control via its two receptors; it induces tumor cell death through lymphotoxin-P receptor (LT-beta R) and ligation to the herpes virus entry mediator (HVEM) amplifies the immune response. By studying the effect of LIGHT in the transcriptional profile of a lymphoid malignancy, we found that HVEM, but not LT-beta R, stimulation induces a significant increase in the expression of chemokine genes such as IL-8, and an unexpected upregulation of apoptotic genes. This had functional consequences, since LIGHT, or HVEM mAb, thus far known to costimulate T- and B-cell activation, induced chronic lymphocytic leukemia cell death. Many of the mediators involved were identified here, with an apoptotic pathway as demonstrated by caspases activation, decrease in mitochondrial membrane potential, upregulation of the pro-apoptotic protein Bax, but also a role of TRAIL. Moreover, HVEM induced endogenous TNF-alpha production and TNF-alpha enhanced HVEM-mediated cell death. HVEM function was mainly dependent on LIGHT, since other ligands like HSV-glycoprotein D and B and T lymphocyte attenuator were essentially ineffective. in conclusion, we describe a novel, as yet unknown killing effect of LIGHT through HVEM on a lymphoid malignancy, and combined with induction of chemokine release this may represent an additional tool to boost cancer immunotherapy
U2 - https://doi.org/10.1002/eji.200939069
DO - https://doi.org/10.1002/eji.200939069
M3 - Article
C2 - 19701890
SN - 0014-2980
VL - 39
SP - 2502
EP - 2514
JO - European journal of immunology
JF - European journal of immunology
IS - 9
ER -