Serpinb9, also known as Proteinase Inhibitor 9 (PI-9), is a well-known endogenous inhibitor of Granzyme B (GzmB) [3]. GzmB is a cytotoxic molecule secreted by cytotoxic T lymphocytes and natural killer cells, and Serpinb9 acts as a protective mechanism against potentially harmful effects of GzmB within the immune system cells. It is involved in immune-related pathways and plays a crucial role in preventing immunopathology, protecting against autoimmune diseases, and regulating cell death [3]. Genetic models, such as KO mouse models, are valuable for studying its functions.

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 the host are deficient in Sb9, demonstrating the potential of Serpinb9 inhibition in controlling tumor growth and increasing survival times in mice [1]. In vivo CRISPR screens in mouse lung cancer models recovered Serpinb9 as an immune evasion factor, suggesting its role in regulating immune therapy response [2].

In conclusion, Serpinb9 is mainly known for its role in inhibiting Granzyme B and is important in immune-related processes. Studies using gene-knockout mouse models have revealed its significant role in tumor-immune evasion and response to immunotherapy, highlighting its potential as a therapeutic target for cancer treatment [1,2].

References:

1. Jiang, Liwei, Wang, Yi-Jun, Zhao, Jing, Dhe-Paganon, Sirano, Abdi, Reza. . Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy. In Cell, 183, 1219-1233.e18. doi:10.1016/j.cell.2020.10.045. https://pubmed.ncbi.nlm.nih.gov/33242418/

2. Dervovic, Dzana, Malik, Ahmad A, Chen, Edward L Y, Jackson, Hartland W, Schramek, Daniel. 2023. In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer. In Nature communications, 14, 3150. doi:10.1038/s41467-023-38841-7. https://pubmed.ncbi.nlm.nih.gov/37258521/

3. Huang, Haozhe, Mu, Yiqing, Li, Song. 2024. The biological function of Serpinb9 and Serpinb9-based therapy. In Frontiers in immunology, 15, 1422113. doi:10.3389/fimmu.2024.1422113. https://pubmed.ncbi.nlm.nih.gov/38966643/