Cosignaling Molecules Around LIGHT-HVEM-BTLA: From Immune Activation to Therapeutic Targeting

The regulation of the immune system at the cell surface is primarily controlled by two families of cosignaling molecules: the immunoglobulin (Ig) superfamily, or ≪CD28 and B7 family≫, and the tumor necrosis factor receptor (TNFR) family. Here, we summarized the principal structural and functional characteristics of both families. In this respect, the interaction between HVEM, a TNF receptor, and BTLA, an Ig family member, has provided a new perspective and an additional level of complexity in the crosstalk between these two regulatory systems. This review will present a summary of the recent advances in the immunobiology of the LIGHT-HVEM-LTβR-BTLA network. The LIGHT-HVEM-BTLA system has emerged as a major regulator of immune responses and lymphocyte activation, whereas LIGHT-LTβR participates in lymphoid tissue development and cell death. Moreover, recent studies have provided encouraging new insights into the roles of the LIGHT-HVEM-LTβR-BTLA axis as a potential target for controlling anti-tumor responses.