LIGHT Proteins (CD258; TNFRSF14) is a type II transmembrane protein produced by activated T cells, belongs to tumor necrosis factor (TNF) family. LIGHT Proteins is a TNFRSF14/HVEM (herpesvirus entry mediator) ligand, engages the receptor for the LTalphabeta heterotrimer but does not form complexes with either secreted lymphotoxin alpha (LTalpha) or LTbeta[1]. LIGHT Proteins is predominantly expressed in the spleen but also found in the brain. And it is weakly expressed in peripheral lymphoid tissues and in heart, placenta, liver, lung, appendix, and kidney, and no expression seen in fetal tissues, endocrine glands, or nonhematopoietic tumor lines[1]. LIGHT Proteins has a transmemberane, thus it can be leaved into 2 chains: tumor necrosis factor ligand superfamily member 14, membrane form and soluble form. The soluble form of isoform 1 derives from the membrane form by proteolytic processing. The protein sequences between human and mouse is different with similarity of 77.22%. In tumor immunology, LIGHT Proteins also serves as a novel immune checkpoint molecule for glioblastoma multiforme (GBM), as well as lung carcinoma, breast carcinoma, cervical cancer, and prostate cancer. LIGHT Proteins can stimulate NK cells to produce IFNγ via nuclear factor-κB (NFκB) RelA/p50 signaling. LIGHT Proteins sustains the function of CD8+ effector T cells, trigger apoptosis of various tumor cells[2]. In cell signaling, LIGHT Proteins binds to lymphotoxin-β receptor (LTβR) and HVEM for activating both of them, and disrupts the HVEM-BTLA complex in surface-bound form, and facilitates HVEM-BTLA complex formation in the soluble form[2]. LIGHT Proteins promotes an inflammatory esophageal fibroblast in vitro via a LTβR-NIK-p52 NF-κB dominant pathway with promoting inflammatory gene expression and down-regulating homeostatic factors including WNTs, BMPs and type 3 semaphorins[3]. Beside that, LIGHT Proteins is a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. LIGHT Proteins also prevents tumor necrosis factor alpha mediated apoptosis in primary hepatocyte[4][5].
