Fig. 3

Interactions of B7-H3 with immune cells and related pathways facilitate B7-H3 function in the microenvironment. The top panel exhibits interactions with immune cells. B7-H3 was originally identified for its effect on promoting the growth of CD4+ T cells and inhibiting the growth of CD8+ T cells. Activated CD4+ T cells induce IFN-γ production and promote the production of IL-12, while IL-2, IL-10, IL-13 and IFN-γ production are suppressed in CD8+ T cells. B7-H3 also negatively regulates the release of IFN-γ and T cell proliferation in B7-H3-deficient mice. B7-H3 suppresses Th1- and Th2-mediated responses, activity and Treg accumulation. IFN-γ and IFN-5 production and Th1-mediated hypersensitivity are inhibited. However, the release of IL-2 and IL-10 is promoted from Th2 cells. B7-H3 enhances M2 macrophage polarization and the release of cytolytic factors from monocytes, which still requires stronger evidence. The cytolytic function of NK cells is curbed. The bottom panel presents distinct pathways to facilitate B7-H3 function. In the TME and related signaling pathways, the roles of B7-H3 are associated with tumor growth, migration, invasion, metastasis and other processes mediated by the PI3K/AKT/mTOR, JAK2/STAT3 and NF-κB signaling pathways and cell metabolism through the TCA cycle. Overall, B7-H3 regulates tumor cell invasion, migration, apoptosis, metabolism and drug response/resistance through classic pathways; B7-H3 also interacts with many types of immune cells in the microenvironment to influence the immune response. TME, tumor microenvironment; TCA cycle, tricarboxylic acid cycle