Gene Set: BUCKANOVICH_T_LYMPHOCYTE_HOMING_ON_TUMOR_UP

Standard name BUCKANOVICH_T_LYMPHOCYTE_HOMING_ON_TUMOR_UP
Systematic name M17086
Brief description Genes up-regulated in microdissected endothelial samples from ovarian cancer tumors with tumor-infiltrating lymphocytes (TIL) vs those without TILs.
Full description or abstract In spite of their having sufficient immunogenicity, tumor vaccines remain largely ineffective. The mechanisms underlying this lack of efficacy are still unclear. Here we report a previously undescribed mechanism by which the tumor endothelium prevents T cell homing and hinders tumor immunotherapy. Transcriptional profiling of microdissected tumor endothelial cells from human ovarian cancers revealed genes associated with the absence or presence of tumor-infiltrating lymphocytes (TILs). Overexpression of the endothelin B receptor (ET(B)R) was associated with the absence of TILs and short patient survival time. The ET(B)R inhibitor BQ-788 increased T cell adhesion to human endothelium in vitro, an effect countered by intercellular adhesion molecule-1 (ICAM-1) blockade or treatment with NO donors. In mice, ET(B)R neutralization by BQ-788 increased T cell homing to tumors; this homing required ICAM-1 and enabled tumor response to otherwise ineffective immunotherapy in vivo without changes in systemic antitumor immune response. These findings highlight a molecular mechanism with the potential to be pharmacologically manipulated to enhance the efficacy of tumor immunotherapy in humans.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18157142   Authors: Buckanovich RJ,Facciabene A,Kim S,Benencia F,Sasaroli D,Balint K,Katsaros D,O'Brien-Jenkins A,Gimotty PA,Coukos G
Exact source Fig. 2B: UP in TIL+
Related gene sets (show 1 additional gene sets from the source publication)

(show 35 gene sets from the same authors)
External links  
Filtered by similarity
Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform HUMAN_SEQ_ACCESSION
Dataset references  
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 21 genes
Gene families Categorize these 21 genes by gene family
Show members (show 31 members mapped to 21 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.