|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
9
|
|
pubmed:dateCreated |
2010-6-28
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/1P01 CA132714,
http://linkedlifedata.com/resource/pubmed/grant/1P01CA100327,
http://linkedlifedata.com/resource/pubmed/grant/1R01NS055140,
http://linkedlifedata.com/resource/pubmed/grant/2P01NS40923,
http://linkedlifedata.com/resource/pubmed/grant/P01 CA100327-01A20001,
http://linkedlifedata.com/resource/pubmed/grant/P01 CA100327-050001,
http://linkedlifedata.com/resource/pubmed/grant/P01 CA132714-01A18081,
http://linkedlifedata.com/resource/pubmed/grant/P01 CA132714-03,
http://linkedlifedata.com/resource/pubmed/grant/P01 NS040923-01A20002,
http://linkedlifedata.com/resource/pubmed/grant/P01 NS040923-06A10005,
http://linkedlifedata.com/resource/pubmed/grant/P01 NS040923-080005,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS055140-01A2,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS055140-03
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Blocking,
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxymethylcellulose Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL10,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Poly I-C,
http://linkedlifedata.com/resource/pubmed/chemical/Polylysine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Interferon alpha-beta,
http://linkedlifedata.com/resource/pubmed/chemical/poly ICLC
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
1432-0851
|
|
pubmed:author |
pubmed-author:Fallert-JuneckoBeth ABA,
pubmed-author:FujitaMitsuguM,
pubmed-author:KalinskiPawelP,
pubmed-author:KastenhuberEdward RER,
pubmed-author:KohanbashGaryG,
pubmed-author:LiuYanY,
pubmed-author:McDonaldHeather AHA,
pubmed-author:OkadaHidehoH,
pubmed-author:ReinhartTodd ATA,
pubmed-author:SalazarAndres MAM,
pubmed-author:UedaRyoR,
pubmed-author:ZhuXinmeiX
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
59
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1401-9
|
|
pubmed:dateRevised |
2011-9-26
|
|
pubmed:meshHeading |
pubmed-meshheading:20549206-Animals,
pubmed-meshheading:20549206-Antibodies, Blocking,
pubmed-meshheading:20549206-Cancer Vaccines,
pubmed-meshheading:20549206-Carboxymethylcellulose Sodium,
pubmed-meshheading:20549206-Cell Line, Tumor,
pubmed-meshheading:20549206-Cell Movement,
pubmed-meshheading:20549206-Central Nervous System Neoplasms,
pubmed-meshheading:20549206-Chemokine CXCL10,
pubmed-meshheading:20549206-Epitopes, T-Lymphocyte,
pubmed-meshheading:20549206-Glioma,
pubmed-meshheading:20549206-Immunization,
pubmed-meshheading:20549206-Interferon-gamma,
pubmed-meshheading:20549206-Mice,
pubmed-meshheading:20549206-Mice, Inbred C57BL,
pubmed-meshheading:20549206-Mice, Knockout,
pubmed-meshheading:20549206-Neoplasm Transplantation,
pubmed-meshheading:20549206-Peptide Fragments,
pubmed-meshheading:20549206-Poly I-C,
pubmed-meshheading:20549206-Polylysine,
pubmed-meshheading:20549206-Receptor, Interferon alpha-beta,
pubmed-meshheading:20549206-T-Lymphocytes, Cytotoxic
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent manners.
|
|
pubmed:affiliation |
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
