Systematic name M1847
Brief description Genes up-regulated in highly immune-resistant cancer cell line developed from a susceptible cancer using an in vivo selection strategy.
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17308126   Authors: Lin KY,Lu D,Hung CF,Peng S,Huang L,Jie C,Murillo F,Rowley J,Tsai YC,He L,Kim DJ,Jaffee E,Pardoll D,Wu TC
Exact source Fig. 1D
Related gene sets (show 16 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jessica Robertson (Broad Institute)
Source platform SEQ_ACCESSION
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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