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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 9/2010

01-09-2010 | Original Article

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

Authors: 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

Published in: Cancer Immunology, Immunotherapy | Issue 9/2010

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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.
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Metadata
Title
Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-α and IFN-γ dependent manners
Authors
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
Publication date
01-09-2010
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 9/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-010-0876-3

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