Serpin family B member 9 (SERPINB9) (SERPINB9)

Serpin B9, also known as Proteinase Inhibitor 9 (PI-9), is a member of the serpin superfamily that serves as the primary endogenous inhibitor of granzyme B, a potent pro-apoptotic serine protease [2, 39]. In healthy physiology, Serpin B9 is expressed by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to protect them from self-inflicted damage by misdirected granzyme B [12, 38]. However, many cancer types, including melanoma and B-cell lymphomas, overexpress Serpin B9 as a mechanism of immune evasion [24, 34]. By neutralizing granzyme B delivered by the immune system, tumor cells become resistant to apoptosis induced by CTLs, NK cells, and chimeric antigen receptor (CAR) T-cell therapies [24, 50]. Consequently, Serpin B9 is an emerging therapeutic target in oncology, with research focusing on small-molecule inhibitors and genetic knockdown strategies to restore the sensitivity of tumors to immunotherapy [4, 29, 49].

Other names

Proteinase inhibitor 9PI-9PI9CAP-3Cytoplasmic antiproteinase 3Serpin B9B9 protein

Serpin B9 acts as a suicide inhibitor of granzyme B. It binds to the active site of granzyme B, forming a stable covalent complex that neutralizes the protease, thereby preventing it from inducing apoptosis in the target cell [4, 24, 29].