Synergizing sunitinib and radiofrequency ablation to treat hepatocellular cancer by triggering the antitumor immune response

Xiaoqiang Qi, Ming Yang, Lixin Ma, Madeline Sauer, DIego Avella, Jussuf T. Kaifi, Jeffrey Bryan, Kun Cheng, Kevin F. Staveley-O'Carroll, Eric T. Kimchi, Guangfu Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Background Minimally invasive radiofrequency ablation (RFA) is used as a first-line treatment option for hepatocellular cancer (HCC) with the weaknesses of incomplete ablation, tumor recurrence, and inferior outcomes. To overcome this limitation, we proposed to develop sunitinib-RFA integrated therapy with a potential of activating anti-HCC immune response. Methods Using our unique murine model, we developed a novel RFA platform with a modified human cardiac RF generator. Therapeutic efficacy of sunitinib-RFA combined treatment in HCC was tested in this platform. Tumor progression was monitored by MRI; tumor necrosis and apoptosis were detected by H&E and terminal deoxynucleotidyl transferase dUTP nick end labeling; immune reaction was defined by flow cytometry; and signaling molecules were examined with real-time PCR (qPCR), western blot, and immunohistochemical staining. Results A significantly reduced tumor growth and extended lift span were observed in the mice receiving combined treatment with RFA and sunitinib. This combined treatment significantly increased the frequency of CD8 + T cell, memory CD8 + T cell, and dendritic cells (DCs); decreased the frequency of regulatory T cells; and activated tumor-specific antigen (TSA) immune response in tumor microenvironment. We found that RFA caused PD-1 upregulation in tumor-infiltrated T cells by boosting hepatocyte growth factor (HGF) expression, which was suppressed by sunitinib treatment. We have also demonstrated that sunitinib suppressed VEGF's effect in enhancing PD-L1 expression in DCs and attenuated heat-sink effect. The results indicate that RFA induced tumor destruction and release of in situ TSAs which can activate a tumoricidal immune response in sunitinib-treated mice, significantly improving anti-HCC therapeutic efficacy. Conclusions Sunitinib enables RFA-released in situ TSA to ignite an effective anti-tumor immune response by suppressing HGF and VEGF signaling pathways. Sunitinib-RFA as a synergistic therapeutic approach significantly suppresses HCC growth.

Original languageEnglish (US)
Article numbere001038
JournalJournal for immunotherapy of cancer
Issue number2
StatePublished - Oct 28 2020


  • combined modality therapy
  • immune tolerance
  • immunomodulation
  • liver neoplasms
  • lymphocytes
  • tumor-infiltrating

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Immunology and Allergy
  • Pharmacology
  • Immunology


Dive into the research topics of 'Synergizing sunitinib and radiofrequency ablation to treat hepatocellular cancer by triggering the antitumor immune response'. Together they form a unique fingerprint.

Cite this