TNFSF14 / LIGHT / CD258, whose name is derived from homologous to lymphotoxins, exhibits inducible expression, and competes with herpes simplex virus (HSV) glycoprotein D for herpesvirus entry mediator (HVEM / TNFRSF14), a receptor expressed by T lymphocytes, is a recently identified member of the human and mouse TNF superfamily. TNFSF14 / LIGHT / CD258 is a 29-kD type II transmembrane protein produced by activated T cells, as well as monocytes and granulocytes, and immature DCs. Apart from its receptor on T cells, HVEM / TNFRSF14, TNFSF14 / LIGHT / CD258 binds to the lymphotoxin β receptor (LTβR) on stromal cells, and the DcR3/TR6 soluble protein.
In vitro, HVEM/LIGHT immune checkpoint pathway induces potent CD28-independent costimulatory activity, leading to NF-κB activation, production of IFN-γ and other cytokines, and T cell proliferation in response to allogeneic DCs. In vivo blockade studies show HVEM/LIGHT immune checkpoint pathway is involved in promotion of cytolytic T cell responses to tumors and the development of GVHD, and transgenic overexpression of TNFSF14 / LIGHT / CD258 within T cells leads to T cell expansion and causes various severe autoimmune diseases.
Qunrui Ye et al. Modulation of LIGHT-HVEM Costimulation Prolongs Cardiac Allograft Survival. J Exp Med. 2002 Mar 18; 195(6): 795–800.
|Co-inhibitory immune checkpoint pathways||Co-stimulatory immune checkpoint pathways|
|PD1 & PD-L1 immune checkpoint pathway||CD40 & CD40L immune checkpoint pathway|
|CTLA-4 & CD80 (CD86) immune checkpoint pathway||OX40 & OX40L immune checkpoint pathway|
|B7-H3 / CD276 immune checkpoint pathway||CD266 & CD155 immune checkpoint pathway|
|B7-H4 / B7S1 / B7x immune checkpoint pathway||CD28 & CD80 (CD86) immune checkpoint pathway|
|HVEM & BTLA immune checkpoint pathway||GITR & GITR Ligand immune checkpoint pathway|
|HVEM & CD160 immune checkpoint pathway||CD27 & CD70 immune checkpoint pathway|
|LAG3 / CD223 / Lymphocyte activation gene 3 immune checkpoint pathway||4-1BB & 4-1BBL immune checkpoint pathway|
|Galectin-9 & TIM-3 immune checkpoint pathway||ICOS & ICOS Ligand immune checkpoint pathway|
|Indoleamine 2,3-dioxygenase/IDO immune checkpoint pathway|
|VISTA / B7-H5 / GI24 immune checkpoint pathway|
|CEACAM1 / CD66a immune checkpoint pathway|
|SIRP alpha & CD47 immune checkpoint pathway|
|2B4 & CD48 immune checkpoint pathway|
|TIGIT & CD155 immune checkpoint pathway|