Tumor Biology

, Volume 36, Issue 3, pp 1561–1566 | Cite as

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

  • Yun Wang
  • Hongxia Li
  • Qi Liang
  • Bin Liu
  • Xiaqi Mei
  • Yingji MaEmail author
Research Article


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.


PD-1 Sorafenib Phosphorylation Therapeutic antibody Oncogene 


Conflicts of interest



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


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yun Wang
    • 1
  • Hongxia Li
    • 1
  • Qi Liang
    • 1
  • Bin Liu
    • 2
  • Xiaqi Mei
    • 3
  • Yingji Ma
    • 1
    Email author
  1. 1.Department of Infectious DiseaseThe Fourth Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Department of Science and EducationHeilongjiang Province Center for Disease Control and PreventionHarbinChina
  3. 3.Department of NeurologyThe Fourth Affiliated Hospital of Harbin Medical UniversityHarbinChina

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