Serpinb9, also known as Proteinase Inhibitor 9 (PI-9), is a well-known endogenous inhibitor of Granzyme B (GzmB). GzmB is a cytotoxic molecule secreted by cytotoxic T lymphocytes and natural killer cells, and Serpinb9 acts as a protective mechanism against the potentially harmful effects of GzmB within immune system cells. It is involved in regulating cell death, preventing immunopathology, and protecting against autoimmune diseases [3].

Genetic ablation of Serpinb9 in mice leads to the death of tumor cells in a granzyme B-dependent manner. Sb9-deficient mice show protective T cell-based host immunity to tumors, along with a decline in GrB-expressing immunosuppressive cells in the tumor microenvironment (TME). Maximum protection against tumor development is seen when both the tumor and host are deficient in Sb9, demonstrating the potential of Serpinb9 inhibition for cancer therapy [1]. In vivo CRISPR screens in mouse lung cancer models also recovered Serpinb9 as an immune evasion factor, indicating its role in governing a tumor's response to immunotherapy [2].

In conclusion, Serpinb9 is a crucial regulator in the immune system, especially in controlling the effects of Granzyme B. Gene knockout mouse models have revealed its significant role in tumor immunity and response to immunotherapy, suggesting that targeting Serpinb9 could be a potential strategy for cancer treatment.