Expression of interleukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma.
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.
Hu
Peng
P
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.
Hu
Huai-Dong
HD
Chen
Min
M
Peng
Ming-Li
ML
Tang
Li
L
Tang
Kai-Fu
KF
Matsui
Masanori
M
Belladonna
Maria Laura
ML
Yoshimoto
Takayuki
T
Zhang
Da-Zhi
DZ
Xiang
Rong
R
Ren
Hong
H
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
C486767:Il27 protein, mouse; D053759:Interleukin-23; D007378:Interleukins; D018664:Interleukin-12; D007371:Interferon-gamma