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Publication : Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy.

First Author  Jiang L Year  2020
Journal  Cell Volume  183
Issue  5 Pages  1219-1233.e18
PubMed ID  33242418 Mgi Jnum  J:298616
Mgi Id  MGI:6477771 Doi  10.1016/j.cell.2020.10.045
Citation  Jiang L, et al. (2020) Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy. Cell 183(5):1219-1233.e18
abstractText  Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner. Sb9-deficient mice exhibited protective T cell-based host immunity to tumors in association with a decline in GrB-expressing immunosuppressive cells within the tumor microenvironment (TME). Maximal protection against tumor development was observed when the tumor and host were deficient in Sb9. The therapeutic utility of Sb9 inhibition was demonstrated by the control of tumor growth, resulting in increased survival times in mice. Our studies describe a molecular target that permits a combination of tumor ablation, interference within the TME, and immunotherapy in one potential modality.
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