title: Expression of interleukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma.
abstract: IL-23 and IL-27 are two novel IL-12 cytokine family members who are quite similar to, but yet clearly distinct from IL-12 in their structures and T-cell stimulatory mechanisms. Here, we demonstrated that either IL-27 or IL-23 has potent antitumor activity in murine models of MM45T.Li hepatocellular carcinoma (HCC). These potent antitumor effects were induced primarily by CD8(+)T cells, secreting IFN-gamma while CD4(+)T cells were also involved as a help of antitumor immunity. However, the antitumor response induced by IL-27 was observed from an early stage of tumor growth whereas that of IL-23 was only evident in the late stage of tumor cell proliferation. IL-23 could induce mice to develop a long-term systemic immunologic memory response against parental MM45T.Li tumors cells, an effect IL-27 was not able to accomplish. CTLs specific for MM45T.Li cells were significantly induced by IL-23, whereas antitumor efficacy mediated by IL-27 and IL-12 involved NK cells, which IL-23 failed to activate. Furthermore, we demonstrated that CD40 expression also plays an important role in the induction of antitumor activities by IL-27, IL-23 or IL-12. Together our data suggest that IL-27 and IL-23 may be two novel and attractive candidate agents to apply to cancer immunotherapy.
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Hu
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Peng
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: Kai-Fu
authors.initials: KF
authors.lastname: Tang
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsui
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Belladonna
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics; D053759:Interleukin-23 / Q000235:genetics* / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics* / Q000627:therapeutic use; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000473:pathology; D014162:Transfection; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: C486767:Il27 protein, mouse; D053759:Interleukin-23; D007378:Interleukins; D018664:Interleukin-12; D007371:Interferon-gamma