Adgre5, also known as CD97, is an adhesion G protein-coupled receptor (aGPCR) that plays significant roles in multiple biological processes. It is involved in regulating cell adhesion, migration, and immune responses. In the immune system, it is related to the homeostasis of dendritic cells in the spleen [3]. It also participates in pathways such as the mitogen-activated protein kinase (MAPK) pathway in glioblastoma cells, promoting glycolytic metabolism [1].

In glioblastoma, CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures both in vitro and in vivo, indicating its role in tumorigenesis [1]. In the context of anti-programmed death-1 (neo-antiPD1) neoadjuvant immunotherapy, an ADGRE5-centered Tsurv model was developed, which can help recognize responders to this immunotherapy by identifying a stem-like CD8+ T cluster with STAT5-ADGRE5 axis enhancement in the tumor microenvironment [2]. CD97-deficient mice are more resistant to RNA virus infection, as CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation [4].

In summary, Adgre5 is crucial in immune regulation, tumor metabolism, and antiviral innate immune responses. Gene knockout models have been instrumental in revealing its role in glioblastoma, response to neoadjuvant cancer immunotherapy, and antiviral immunity, providing insights for potential therapeutic strategies in these disease areas.