Mouse Gene Set: ZENG_GU_ICB_CONTROL_METAGENE_31_PRECICTIVE_ICB_RESISTANCE


Standard name ZENG_GU_ICB_CONTROL_METAGENE_31_PRECICTIVE_ICB_RESISTANCE
Systematic name MM17086
Brief description Metagene_31 is enriched in LIHC, which has a low response rate to ICB treatment (Fig. 4D). Metagene_31 is also highly enriched in the syngeneic mouse models that are resistant to ICB treatment (Fig. 2C). The top genes in metagene_31 include Col2a1, Col9a1/2, and Sox8 (Fig. 5F and table S5), and enriched pathways include extracellular matrix (ECM) receptor interactions and collagens (Fig. 5, G and H). Sox8 is a transcription factor involved in embryogenesis and is highly expressed in most hepatocellular carcinomas, where it has been shown to promote tumor cell proliferation (41). Tumor Immune Dysfunction and Exclusion (TIDE) (8) analysis suggested that Sox8 is highly expressed in alternatively activated M2 tumor-associated macrophages (TAMs), which restrict intratumoral CTL infiltration. Col2a1 encodes the alpha-1 chain of type II collagen, a component of the ECM. Collagen induction has also been reported to confer immune evasion by physically impeding CTL infiltration (42). Moreover, metagene_31 level was positively correlated with the gene signature of alternatively activated M2 TAMs (Fig. 5I), which suppress CTL response (43).
Full description or abstract Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, [this study] developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, [this study] found that the model can predict clinical ICB response. [This study] further applied the model to predicting ICB-responsive/resistant cancer types in The Cancer Genome Atlas, which agreed well with existing clinical reports.
Collection M2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 36240281   Authors: Zeng Z,Gu SS,Wong CJ,Yang L,Ouardaoui N,Li D,Zhang W,Brown M,Liu XS
Exact source Table S5. Top genes in different metagenes (control samples): metageneor31
Related gene sets (show 12 additional gene sets from the source publication)

(show 10 gene sets from any of these authors)
External links http://tismo.cistrome.org/
Filtered by similarity ?
Source species Mus musculus
Contributed by Anthony Castanza (MSigDB Team)
Source platform or
identifier namespace		 MOUSE_GENE_SYMBOL
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
Mouse Transcriptomic BodyMap compendium

Legacy heatmaps (PNG)
Mouse Transcriptomic BodyMap compendium
Advanced query Further investigate these 200 genes
Show members (show 200 source identifiers mapped to 200 genes)
Version history 2023.2.Mm: First Introduced.

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