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- 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; Fallert-Junecko, Beth A.; Mitsugu Fujita; Ryo Ueda; Kohanbash, Gary; Kastenhuber, Edward R.; McDonald, Heather A.; Yan Liu; Kalinski, Pawel; Reinhart, Todd A.; Salazar, Andres M.; Hideho Okada
- 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.
- Publication
Cancer Immunology, Immunotherapy, 2010, Vol 59, Issue 9, p1401
- ISSN
0340-7004
- Publication type
Academic Journal
- DOI
10.1007/s00262-010-0876-3