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
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Source species Mus musculus
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