Background Herpesvirus Entry Mediator (HVEM, also referred to in the literature as HveA) is a member of the tumor necrosis factor receptor superfamily, also known as tumor necrosis factor receptor superfamily 14 (TNFRSF14). HVEM and BTLA, LIGHT, CD160, CD5, HSV gD and other components form a sophisticated network. The HVEM network is a bidirectional regulatory network in which stimulatory and inhibitory coexist. HVEM is closely related to immune response, tumor, inflammation, and transplant rejection, and is a valuable and promising immunotherapy target. In recent years, scholars have paid increasing attention to HVEM,the present work aimed to summarizes the relationship between HVEM and immunity and summarizes the phased results of HVEM research in recent years and put forward some possible research ideas and directions.

Materials and Methods We have consulted multiple sources and read almost all the relevant literature on HVEM immunity in recent years. We have written according to several parts such as HVEM and T cells, B cells, tumors, inflammation, immune rejection, and other diseases. We have sorted out and summarized the close relationship between HVEM and immune cells and immune diseases, providing promising ideas for immunotherapy, and making efforts to reveal the HVEM signaling system and research new targets.

Conclusions HVEM plays a role in suppressing tumor immunity in lung cancer, ovarian cancer, glioblastoma and hepatocellular carcinoma. [16, 28-30]. HVEM also has also been shown to be associated with poor prognosis in follicular lymphoma, glioblastoma(GBM), gastric, breast and renal clear cell carcinoma[29, 31-34]. In contrast, HVEM has been shown to play a positive role in bladder cancer, endometrial cancer, and melanoma[40, 41]. In primary cutaneous follicular center lymphoma, primary diffuse large B-cell lymphoma of bone, diffuse large B-cell lymphoma (DLBCL), mucosa-associated lymphoid tissue (MALT) lymphoma, and primary cutaneous anaplastic In large cell lymphomas, HVEM has been detected with varying degrees of mutation[42-47], the scientific application of genetic engineering may play a unique role in the treatment of these diseases. In the inflammatory response, due to the specificity of HVEM, it exhibits both anti-inflammatory and pro-inflammatory effects. The addition of both anti- and pro-inflammatory effects of BTLA and LIGHT complicates the role of HVEM in the inflammatory response[15]. The relationship between HVEM ligand and rejection of human immune transplantation is still less studied, Ye et al. found that the co-stimulation of T cells by LIGHT-HVEM is an important reason for the immune rejection of host heart transplantation[70], This may provide an idea for improving the success rate of heart transplants. indicating that cutting or blocking the connection between LIGHT and HVEM may improve the success rate of heart transplantation. In general, HVEM is closely related to immune response, tumor, inflammation, and transplant rejection, and is a valuable and promising immunotherapy target. Conclusions need to be drawn on the basis of more scientific experiments to mine the role of HVEM in human immunity.

J. xia: None. Z. xia: None. K. xiao: None.