Background Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat. The interleukin (IL)‐12 family cytokines, including IL‐12, IL‐23 and IL‐27, display overlapping, but not redundant, roles in regulating lymphocyte subpopulations. IL‐12 is known as a potent antitumor cytokine, whereas the results of the antitumor effect of IL‐23 and IL‐27 are inconsistent. The present study aimed to directly compare the relative antitumor efficacy of these three IL‐12 family cytokines on HCC. Methods A murine orthotopic BNL HCC model, in which the tumor is located in an environment heavily populated with different lymphocyte subsets, was established. The hepatotropic adeno‐associated virus serotype 8 (AAV8) vector was used to deliver the cytokine genes aiming to achieve sustained cytokine expression in the liver. Results AAV8/IL‐12 treatment significantly reduced hepatic metastases and prolonged survival time, whereas treatment with AAV8/IL‐23 or AAV8/IL‐27 had only moderate antitumor effects at a high dose. The antitumor efficacy of these cytokines was positively correlated with their ability to regulate hepatic T cells, natural killer cells and natural killer T cells, with IL‐12 greatly increasing the number and activation status of these cells, whereas IL‐27 had no effect and IL‐23 had a negative effect. AAV8/IL‐12 treatment also resulted in a marked decrease in tumor vessel density, which was not observed with AAV8/IL‐23 and AAV8/IL‐27 treatment. Conclusions The data obtained in the present study highlight the importance of local lymphocytes and anti‐angiogenesis for influencing the antitumor activity of these three IL‐12 family cytokines and suggest that IL‐12 is the best candidate for treating HCC. Copyright © 2010 John Wiley & Sons, Ltd.
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Differential antitumor effect of interleukin‐12 family cytokines on orthotopic hepatocellular carcinoma
Lo, Chia‐Hui; Chang, Chia‐Ming; Tang, Shih‐Wen; Pan, Wen‐Yu; Fang, Cheng‐Chieh; Chen, Yin; Wu, Ping‐Yi; Chen, Kai‐Yun; Ma, Hsin‐I; Xiao, Xiao; Tao, Mi‐Hua
Follow Journal of Gene Medicine
, Volume 12 (5)
Wiley – May 1, 2010
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