Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice

Cancer Immunol Immunother. 2011 May;60(5):671-83. doi: 10.1007/s00262-011-0984-8. Epub 2011 Feb 16.


Toll-like receptor (TLR) agonists can trigger broad inflammatory responses that elicit rapid innate immunity and promote the activities of lymphocytes, which can potentially enhance adoptive immunotherapy in the tumor-bearing setting. In the present study, we found that Polyinosinic:Polycytidylic Acid [Poly(I:C)] and CpG oligodeoxynucleotide 1826 [CpG], agonists for TLR 3 and 9, respectively, potently activated adoptively transferred T cells against a murine model of established melanoma. Intratumoral injection of Poly(I:C) and CpG, combined with systemic transfer of activated pmel-1 T cells, specific for gp100(25-33), led to enhanced survival and eradication of 9-day established subcutaneous B16F10 melanomas in a proportion of mice. A series of survival studies in knockout mice supported a key mechanistic pathway, whereby TLR agonists acted via host cells to enhance IFN-γ production by adoptively transferred T cells. IFN-γ, in turn, enhanced the immunogenicity of the B16F10 melanoma line, leading to increased killing by adoptively transferred T cells. Thus, this combination approach counteracted tumor escape from immunotherapy via downregulation of immunogenicity. In conclusion, TLR agonists may represent advanced adjuvants within the setting of adoptive T-cell immunotherapy of cancer and hold promise as a safe means of enhancing this approach within the clinic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Immunotherapy, Adoptive*
  • Inflammation
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligodeoxyribonucleotides / therapeutic use*
  • Poly I-C / therapeutic use*
  • T-Lymphocytes / immunology*
  • Toll-Like Receptors / agonists*
  • Toll-Like Receptors / immunology


  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • Toll-Like Receptors
  • Interferon-gamma
  • Poly I-C