Intratumoural GM-CSF microspheres and CTLA-4 blockade enhance the antitumour immunity induced by thermal ablation in a subcutaneous murine hepatoma model

Int J Hyperthermia. 2009 Aug;25(5):374-82. doi: 10.1080/02656730902976807.


Purpose: We evaluated the effect of a new antitumour immunity regimen that included microwave ablation, intratumoural microspheres encapsulating granulocyte-macrophage colony stimulating factor (GM-CSF), and blockade of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4).

Materials and methods: C57BL6 mice with an established subcutaneous Hepa 1-6 hepatoma underwent microwave ablation, followed by intratumoural injection of GM-CSF microspheres, and intraperitoneal injection of anti-CTLA-4 antibodies. The therapeutic effects were evaluated by tumour growth, survival analysis, and cytotoxicity of T lymphocytes against Hepa 1-6.

Results: The co-administration of microwave thermal ablation, GM-CSF microspheres, and anti-CTLA-4 rejected tumour rechallenge in 90% of treated mice in a subcutaneous murine Hepa 1-6 model, and cured established distant tumour in 50% of the treated mice. This antitumour immune response was tumour-specific and mediated by natural killer (NK), CD4+, and CD8+ T cells.

Conclusions: Microwave ablation, followed by intratumoural GM-CSF microspheres, and anti-CTLA-4 antibodies results in the local eradication of tumours, rejection of tumours following rechallenge, and cures established distant tumours, suggesting that this is a promising regimen and one that is readily applicable in the clinic.

MeSH terms

  • Animals
  • Antigens, CD / immunology*
  • CTLA-4 Antigen
  • Combined Modality Therapy
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / radiotherapy
  • Liver Neoplasms, Experimental / therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microspheres
  • Microwaves / therapeutic use*


  • Antigens, CD
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Granulocyte-Macrophage Colony-Stimulating Factor