Vtcn1, also known as B7-H4, B7S1, and B7x, is an immune checkpoint belonging to the B7 superfamily. It negatively regulates T-cell activation and is involved in multiple biological processes such as tumorigenesis, immune tolerance, and autoimmune diseases [1]. Dysregulation of Vtcn1 has been linked to the exacerbation of autoimmune diseases, and its increased soluble form in patient sera correlates with disease progression [1].

Genetic deficiency of B7-H4 (Vtcn1) in allogeneic pregnancy models led to immune activation and fetal resorption, indicating its role in onco-fetal immune tolerance [2]. In cancer, Vtcn1 promotes tumor progression. For example, in breast cancer, it contributes to cancer progression accompanied by CD8+ T cell exhaustion [2]. In ovarian carcinoma, low expression of Vtcn1 could inhibit the viability and metastasis of the carcinoma both in vitro and in vivo, and it was found to affect the cell cycle and JAK2/STAT signaling pathways [3].

In summary, Vtcn1 plays a crucial role in immune regulation, onco-fetal immune tolerance, and cancer progression. The use of gene knockout models in mice has revealed its significance in these biological processes and disease conditions, especially in autoimmune diseases and cancer, providing potential therapeutic targets for these diseases.