Regression of primary hepatocarcinoma in cancer-prone transgenic mice by local interferon-gamma delivery is associated with macrophages recruitment and nitric oxide production

Cancer Gene Therapy
M BaratinJ G Guillet

Abstract

The clinical potential of tumor therapies must be evaluated using animal models closely resembling human cancers. We investigated the impact of locally delivered interferon-gamma (IFN-gamma) on primary hepatocarcinoma spontaneously developed by T-SV40 transgenic mice. A single intratumor injection of adenovirus IFN-gamma was sufficient enough to induce in vivo production of biologically active IFN-gamma, as assessed by STAT1 activation. IFN-gamma secretion led to the regression of primary tumor, principally by apoptosis of tumor hepatocytes. The lack of T-cells infiltrates in the liver upon treatment excluded a role of a specific immune response. In contrast, indirect pathways may include tumoricidal function of macrophages. Indeed, they were massively recruited in the entire liver under IFN-gamma treatment; transmigration through hepatic blood vessels could be observed and co-localization with damaged hepatocytes was obvious. This correlated with nonparenchymal liver cell iNOS expression and high level of NO in hepatic extracts. Moreover, in vitro experiments showed that NO releasing agents induced cell death of freshly isolated tumor hepatocytes, suggesting that NO could be one of the major effector molecules. Altogether, the...Continue Reading

Citations

Dec 30, 2006·Apoptosis : an International Journal on Programmed Cell Death·Rebecca L VanOostenThomas S Griffith
Mar 12, 2004·Journal of Gastroenterology and Hepatology·Jean-Marie PeronGilles Favre
Sep 23, 2006·Medicinal Research Reviews·Simone MocellinDonato Nitti
Sep 15, 2005·Cancer Letters·Dan-Qing LouCatherine Cavard
May 4, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·K Hansen, C Khanna
Jul 16, 2008·Seminars in Cell & Developmental Biology·Gabriella RegisValeria Poli
Dec 17, 2014·International Immunopharmacology·Mahmoud Abdel-LatifAl-Mahy El-Mallah
Dec 26, 2001·Oncogene·M T Sáenz-RoblesJ M Pipas
Oct 13, 2006·World Journal of Gastroenterology : WJG·Ruben Hernandez-AlcocebaJesus Prieto
May 20, 2020·Therapeutic Advances in Medical Oncology·Jinguo ZhangGuoxiong Xu
Oct 8, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elodie BelnoueMireille Viguier

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