title: Anti-angiogenic therapy renders large tumors vulnerable to immunotherapy via reducing immunosuppression in the tumor microenvironment.
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.
authors.affiliation: Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Suit-Fong
authors.initials: SF
authors.lastname: Chan
authors.forename: Hao-Tien
authors.initials: HT
authors.lastname: Wang
authors.forename: Kai-Wen
authors.initials: KW
authors.lastname: Huang
authors.forename: Pao-Ling
authors.initials: PL
authors.lastname: Torng
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Lee
authors.forename: Lih-Hwa
authors.initials: LH
authors.lastname: Hwang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D043169:Endostatins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology / Q000628:therapy; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D043169:Endostatins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor