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

Xinmei Zhu, Beth A. Fallert-Junecko, Mitsugu Fujita, Ryo Ueda, Gary Kohanbash, Edward R. Kastenhuber, Heather A. McDonald, Yan Liu, Pawel Kalinski, Todd A. Reinhart, Andres M. Salazar, Hideho Okada

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

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-α and IFN-γ 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-α receptor-1 (IFN-αR1)-/- or IFN-γ -/- 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-αR -/- and IFN-γ -/- 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-γ. Our data point to critical roles of the host-IFN-α and IFN-γ pathways in the modulation of CNS glioma microenvironment, and the therapeutic effectiveness of poly-ICLC-assisted glioma vaccines.

Original languageEnglish
Pages (from-to)1401-1409
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume59
Issue number9
DOIs
Publication statusPublished - 2010 Sep
Externally publishedYes

Keywords

  • CNS glioma
  • Chemokine
  • Glioma vaccine
  • Poly-ICLC
  • Type-1 immune response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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