Anti-angiogenic therapy renders large tumors vulnerable to immunotherapy via reducing immunosuppression in the tumor microenvironment
Journal
Cancer Letters
Journal Volume
320
Journal Issue
1
Pages
23-30
Date Issued
2012
Author(s)
Abstract
We have recently demonstrated that a 4-in-1 gene therapy strategy that contains two anti-angiogenic genes [endostatin and pigment epithelium-derived factor] and two cytokine genes [granulocyte macrophage colony-stimulating factor and interleukin 12] has a considerable antitumor effect on large tumors in a woodchuck hepatoma model. The current study further investigates the underlying mechanisms for the antitumor effect observed by using small rodent models. We found that immunotherapy alone increased immunosuppressive cells in large tumors over time, whereas the anti-angiogenic therapy contained in the 4-in-1 strategy alleviated immunosuppression and made tumors vulnerable to immunotherapy, thus resulting in a synergistic antitumor effect. ? 2012 Elsevier Ireland Ltd.
SDGs
Other Subjects
endostatin; granulocyte macrophage colony stimulating factor; interleukin 12; pigment epithelium derived factor; animal cell; animal experiment; animal model; animal tissue; antiangiogenic gene therapy; article; cancer gene therapy; cancer immunotherapy; drug potentiation; embryo; human; human cell; immune deficiency; immunocompetent cell; liver cell carcinoma; mouse; nonhuman; priority journal; tumor microenvironment; tumor volume; Adenoviridae; Animals; Apoptosis; Cell Line, Tumor; Combined Modality Therapy; Endostatins; Eye Proteins; Gene Therapy; Humans; Immunotherapy; Liver Neoplasms, Experimental; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Nerve Growth Factors; Serpins; T-Lymphocytes, Regulatory; Tumor Microenvironment; Adenoviridae; Marmota monax; Rodentia