Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent manners

Cancer Immunol Immunother. 2010 Sep;59(9):1401-9. doi: 10.1007/s00262-010-0876-3. Epub 2010 Jun 12.


Stimulation of double-stranded (ds)RNA receptors can increase the effectiveness of cancer vaccines, but the underlying mechanisms are not completely elucidated. In this study, we sought to determine critical roles of host IFN-alpha and IFN-gamma pathways in the enhanced therapeutic efficacy mediated by peptide vaccines and polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in the murine central nervous system (CNS) GL261 glioma. C57BL/6-background wild type (WT), IFN-alpha receptor-1 (IFN-alphaR1)(-/-) or IFN-gamma(-/-) mice bearing syngeneic CNS GL261 glioma received subcutaneous (s.c.) vaccinations with synthetic peptides encoding CTL epitopes with or without intramuscular (i.m.) injections of poly-ICLC. The combinational treatment induced a robust transcription of CXCL10 in the glioma site. Blockade of CXCL10 with a specific monoclonal antibody (mAb) abrogated the efficient CNS homing of antigen-specific type-1 CTL (Tc1). Both IFN-alphaR(-/-) and IFN-gamma(-/-) hosts failed to up-regulate the CXCL10 mRNA and recruit Tc1 cells to the tumor site, indicating non-redundant roles of type-1 and type-2 IFNs in the effects of poly-ICLC-assisted vaccines. The efficient trafficking of Tc1 also required Tc1-derived IFN-gamma. Our data point to critical roles of the host-IFN-alpha and IFN-gamma pathways in the modulation of CNS glioma microenvironment, and the therapeutic effectiveness of poly-ICLC-assisted glioma vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / administration & dosage
  • Cancer Vaccines*
  • Carboxymethylcellulose Sodium / administration & dosage
  • Carboxymethylcellulose Sodium / analogs & derivatives*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Central Nervous System Neoplasms / immunology
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / therapy*
  • Chemokine CXCL10 / biosynthesis
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • Epitopes, T-Lymphocyte / chemistry
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy*
  • Immunization
  • Interferon-gamma / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Transplantation
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemistry
  • Poly I-C / administration & dosage*
  • Polylysine / administration & dosage
  • Polylysine / analogs & derivatives*
  • Receptor, Interferon alpha-beta / genetics
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / pathology


  • Antibodies, Blocking
  • Cancer Vaccines
  • Chemokine CXCL10
  • Epitopes, T-Lymphocyte
  • Peptide Fragments
  • Receptor, Interferon alpha-beta
  • Polylysine
  • poly ICLC
  • Interferon-gamma
  • Carboxymethylcellulose Sodium
  • Poly I-C