Direct Tumor Killing and Immunotherapy through Anti-SerpinB9 Therapy.

Autor:	Jiang L; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Wang YJ; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Zhao J; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Uehara M; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Hou Q; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Qingdao 266071, China., Kasinath V; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Ichimura T; Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Banouni N; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Dai L; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Li X; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Greiner DL; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA., Shultz LD; The Jackson Laboratory, Bar Harbor, ME 04609, USA., Zhang X; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China., Sun ZJ; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Curtin I; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Vangos NE; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Yeoh ZC; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Geffken EA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Seo HS; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Liu ZX; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China., Heffron GJ; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA., Shah K; Center for Stem Cell Therapeutics and Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA., Dhe-Paganon S; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Abdi R; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: rabdi@rics.bwh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2020 Nov 25; Vol. 183 (5), pp. 1219-1233.e18.
DOI:	10.1016/j.cell.2020.10.045
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare they have no competing interests. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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