Fig. 6

Immunology and future clinical immunotherapy of B7-H3. In T cells, OX40 liganded by OX40 L and the CD4/TCR-MHC II-antigen peptide complex elicit the following signals with a number of well-established proinflammatory mediators, such as PI3K, AKT, NFκB and ERK. Through the PI3K/AKT pathway, many downstream signatures are activated, including NFκB, IL-2 production, mTOR activation and Bcl-xl activation. Then, activated NFκB stimulates the release of cytokines and chemokines. The activation of the TGFβ receptor can inhibit the maturation of miR-21 and enhance PDCD4 levels. The translation of the anti-inflammatory cytokine IL-10 is suppressed in this signal, and the level is downregulated. TGFβ1 can participate in the adhesion, migration and invasion of renal cell carcinoma (RCC) cells. Clinical immunotherapy targeting B7-H3 includes blockade of B7-H3 monoclonal antibodies (mAbs), although the ligand is unclear; B7-H3-specific antibody‒drug conjugates (ADCs); B7-H3-specific antibody-dependent cell-mediated cytotoxicity (ADCC); B7-H3 and CD3 bispecific antibodies; engineered chimeric antigen receptor T cells (CAR-T cells); radionucleotides-induced radioimmunotherapy; other combined therapies (combined with PD-L1, PD-L2, etc.)