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Combinatorial immunotherapy of sorafenib and blockade of programmed death-ligand 1 induces effective natural killer cell responses against hepatocellular carcinoma

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Tumor Biology

Abstract

Sorafenib, a multi-tyrosine kinase inhibitor, is a standard treatment for advanced hepatocellular carcinoma (HCC). Herein, we report that the combinatorial therapy of sorafenib and anti-programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) can be implemented with good results for HCC. Cancer mouse models were used to evaluate therapeutic efficacy and examine the immunologic mechanisms of the sorafenib/anti-PD-L1 mAb therapy. The combined administration of sorafenib and anti-PD-L1 mAb into tumor-bearing mice generated potent immune responses resulting in the complete eradication or remarkable reduction of tumor growth. In some instances, the sorafenib/anti-PD-L1 mAb therapy induced long-lasting protection against tumor rechallenges. The results indicate that NK cells but not CD4T cells or CD8 cells mediated the therapeutic efficacy of this combinatorial therapy. The overall results suggest that immunotherapy consisting of the combination of sorafenib/anti-PD-L1 mAb could be a promising new approach for treating patients with HCC.

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Conflicts of interest

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Funding

Heilongjiang Province Natural Science Fund Project (D207016) Fund project of Heilongjiang Province Education Office (11501250).

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Authors and Affiliations

  1. Department of Infectious Disease, The Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Street, Nangang District, Harbin, 150001, China

    Yun Wang, Hongxia Li, Qi Liang & Yingji Ma

  2. Department of Science and Education, Heilongjiang Province Center for Disease Control and Prevention, Harbin, 150036, China

    Bin Liu

  3. Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China

    Xiaqi Mei

Authors
  1. Yun Wang
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  2. Hongxia Li
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  3. Qi Liang
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  4. Bin Liu
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  5. Xiaqi Mei
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  6. Yingji Ma
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Correspondence to Yingji Ma.

Additional information

Yun Wang, Hongxia Li and Qi Liang are contributed equally to this work.

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Wang, Y., Li, H., Liang, Q. et al. Combinatorial immunotherapy of sorafenib and blockade of programmed death-ligand 1 induces effective natural killer cell responses against hepatocellular carcinoma. Tumor Biol. 36, 1561–1566 (2015). https://doi.org/10.1007/s13277-014-2722-2

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  • DOI: https://doi.org/10.1007/s13277-014-2722-2

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