Tumor necrosis factor ligand superfamily member 14 (LIGHT) (TNFSF14)

Tumor necrosis factor ligand superfamily member 14 (TNFSF14), commonly known as LIGHT, is a potent cytokine that coordinates immune responses by binding to two functional receptors: Herpesvirus Entry Mediator (HVEM) and Lymphotoxin beta receptor (LTβR) [4, 6, 12]. Primarily expressed on activated T cells, natural killer cells, and immature dendritic cells, LIGHT acts as a costimulatory signal for T-cell proliferation and the release of pro-inflammatory cytokines like IL-12 and IL-13 [1, 11, 12]. In chronic inflammatory diseases such as asthma and inflammatory bowel disease (IBD), overexpression of LIGHT drives pathological tissue remodeling, airway smooth muscle hyperplasia, and mucosal damage [1, 9, 14]. Conversely, in the tumor microenvironment, LIGHT expression can promote anti-tumor immunity by normalizing tumor vasculature and inducing the formation of high endothelial venules, which facilitate the infiltration of effector T cells [4, 16, 17]. Clinical development focuses on neutralizing monoclonal antibodies, such as quisovalimab (AVTX-002), which block LIGHT to reduce inflammation in asthma and COVID-19-related respiratory failure [2, 9, 12]. However, therapeutic targeting is complicated by the LIGHT-signaling network's interaction with other checkpoints, such as BTLA and CD160, which compete for HVEM binding and provide inhibitory signals that must be carefully balanced to avoid unintended immune activation or suppression [3, 12, 14].

Other names

LIGHTCD258HVEMLLTgTR2Herpesvirus entry mediator ligandTumor necrosis factor ligand superfamily member 14

Neutralizing monoclonal antibodies bind to soluble and membrane-bound TNFSF14, preventing its interaction with receptors HVEM and LTβR to dampen inflammatory signaling and tissue remodeling [1, 9, 12]. Alternatively, bifunctional fusion proteins act as agonists to stimulate these receptors to enhance anti-tumor immunity [4, 16].