The involvement of semaphorin 7A in tumorigenic and immunoinflammatory regulation

Semaphorins, a large group of highly conserved proteins, consist of eight subfamilies that are widely expressed in vertebrates, invertebrates, and viruses and exist in membrane-bound or secreted forms. First described as axon guidance cues during neurogenesis, semaphorins also perform physiological functions in other organ systems, such as bone homeostasis, immune response, and tumor progression. Semaphorin 7A (SEMA7A), also known as CDw108, is an immune semaphorin that modulates diverse immunoinflammatory processes, including immune cell interactions, inflammatory infiltration, and cytokine production. In addition, SEMA7A regulates the proliferation, migration, invasion, lymph formation, and angiogenesis of multiple types of tumor cells, and these effects are mediated by the interaction of SEMA7A with two specific receptors, PLXNC1 and integrins. Thus, SEMA7A is intimately related to the pathogenesis of multiple autoimmune and inflammation-related diseases and tumors. This review focuses on the role of SEMA7A in the pathogenesis of autoimmune disorders, inflammatory diseases, and tumors, as well as the underlying mechanisms. Furthermore, strategies targeting SEMA7A as a potential predictive, diagnostic, and therapeutic agent for these diseases are also addressed.