STANDARD_NAME	LIN_TUMOR_ESCAPE_FROM_IMMUNE_ATTACK
SYSTEMATIC_NAME	M1847
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LIN_TUMOR_ESCAPE_FROM_IMMUNE_ATTACK
NAMESPACE	MOUSE_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes up-regulated in highly immune-resistant cancer cell line developed from a susceptible cancer using an in vivo selection strategy.
DESCRIPTION_FULL	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.
PMID	17308126
GEOID	GSE2774
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
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Fig. 1D
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AA472735,AK005158,AK009098,AK014353,AK015397,AV359819,BB075339,BB126999,BB250384,BB332449,BB662927,BC005560,BC015254,BG084683,BQ176723,L20048,NM_008127,NM_008726,NM_011619,NM_018784,NM_019564,NM_134066,U94828,X75557
GENE_SYMBOLS	MMD,PLA2G7,DYNAP,KHDRBS3,C14orf39,JAG1,GPR149,GPR149,VCAM1,,,SYCP3,ACKR3,CHD7,NRP2,IL2RG,GJB4,NPPB,TNNT2,ST3GAL6,HTRA1,,RGS16,
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