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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2007-2-19
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pubmed:abstractText |
Immune escape is an important reason why the immune system cannot control tumor growth, but how escape variants emerge during immunotherapy remains poorly understood. Here, we identify a new mechanism of tumor immune escape using an in vivo selection strategy. We generated a highly immune-resistant cancer cell line (P3) by subjecting a susceptible cancer cell line (P0/TC-1) to multiple rounds of in vivo immune selection. Microarray analysis of P0 and P3 revealed that vascular cell adhesion molecule-1 (VCAM-1) is up-regulated in the P3-resistant variant. Retroviral transfer of VCAM-1 into P0 significantly increased its resistance against a vaccine-induced immune response. Analysis of tumors showed a dramatic decrease in the number of tumor-infiltrating cluster of differentiation 8(+) (CD8(+)) T cells in the tumors expressing VCAM-1. In vitro transwell migration assays showed that VCAM-1 can promote the migration of CD8(+) T cells through its interaction with the alpha(4)beta(1) integrin. Site-directed mutagenesis of VCAM-1 at amino acid residues required for interaction with alpha(4)beta(1) integrin completely abolished the immune resistance conferred by VCAM-1 in vivo. Surface staining showed that most renal cell carcinomas (RCC) express VCAM-1, whereas an RCC that responded to vaccination was VCAM-1 negative. These data provide evidence that tumor expression of VCAM-1 represents a new mechanism of immune evasion and has important implications for the development of immunotherapy for human RCC.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0008-5472
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pubmed:author |
pubmed-author:AusGG,
pubmed-author:HeLiangmeiL,
pubmed-author:HuangLanqingL,
pubmed-author:HungChien-FuCF,
pubmed-author:JaffeeElizabethE,
pubmed-author:JieChunfaC,
pubmed-author:KimDae-JinDJ,
pubmed-author:LinKen-YuKY,
pubmed-author:MurilloFranciscoF,
pubmed-author:PardollDrewD,
pubmed-author:PengShiwenS,
pubmed-author:RowleyJesseJ,
pubmed-author:TsaiYa-CheaYC,
pubmed-author:UeoKK
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1832-41
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:17308126-Animals,
pubmed-meshheading:17308126-Apoptosis,
pubmed-meshheading:17308126-Binding Sites,
pubmed-meshheading:17308126-CD8-Positive T-Lymphocytes,
pubmed-meshheading:17308126-Cell Movement,
pubmed-meshheading:17308126-Down-Regulation,
pubmed-meshheading:17308126-Immunotherapy,
pubmed-meshheading:17308126-Integrin alpha4beta1,
pubmed-meshheading:17308126-Mice,
pubmed-meshheading:17308126-Mice, Inbred C57BL,
pubmed-meshheading:17308126-Neoplasms, Experimental,
pubmed-meshheading:17308126-Oncogene Proteins, Viral,
pubmed-meshheading:17308126-Papillomavirus E7 Proteins,
pubmed-meshheading:17308126-Repressor Proteins,
pubmed-meshheading:17308126-Up-Regulation,
pubmed-meshheading:17308126-Vaccinia virus,
pubmed-meshheading:17308126-Vascular Cell Adhesion Molecule-1
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pubmed:year |
2007
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pubmed:articleTitle |
Ectopic expression of vascular cell adhesion molecule-1 as a new mechanism for tumor immune evasion.
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pubmed:affiliation |
Department of Pathology, Institute of Genetic Medicine, Johns Hopkins Medical Institutions, 1550 Orleans Street, Baltimore, MD 21231, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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