ArticleJournal for immunotherapy of cancer2022
Wilms tumor reveals DNA repair gene hyperexpression is linked to lack of tumor immune infiltration.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Topical TLR7 agonist and radiotherapy in patients with metastatic breast cancer.Journal for immunotherapy of cancer · 2025Trial
- The absence of Trim28 in nephron progenitors results in impaired kidney development and function.Development (Cambridge, England) · 2026Article
- Genetic Variants in BER Pathway Genes Confer Wilms Tumor Susceptibility: New Insights from an Eight-Center Case-Control Study in Chinese Children.Annals of surgical oncology · 2026Article
- SNRPC promotes chemoresistance in Wilms tumor via the NF-κB-CXCL17 axis regulating M2-Type TAMs infiltration and targeted nanotherapy research.Journal of experimental & clinical cancer research : CR · 2026Article
- Cross-cancer transcriptomic analysis reveals conserved developmental, ferroptosis, and immune remodeling modules in Wilms tumor and oral cancer.Frontiers in genetics · 2026Article
- PD-L1 Expression is Mediated by microRNA Processing, Wnt/β-Catenin Signaling, and Chemotherapy in Wilms Tumor.Pediatric blood & cancer · 2025Article
- The signature based on interleukin family and receptors identified IL19 and IL20RA in promoting nephroblastoma progression through STAT3 pathway.Scientific reports · 2025Article
- NK cell-related genes-driven novel molecular subtyping and prognostic signatures for Wilms tumor: uncovering the therapeutic potential of TGX-221 and biomarker role of HS2ST1.Frontiers in oncology · 2025Article
- Construction of a Wilms tumor risk model based on machine learning and identification of cuproptosis-related clusters.BMC medical informatics and decision making · 2024Article
- Identification of potential novel N6-methyladenosine effector-related lncRNA biomarkers for serous ovarian carcinoma: a machine learning-based exploration in the framework of 3P medicine.Frontiers in pharmacology · 2024Article
- Review
- Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 2nd - 4th, 2021, Italy).Journal of translational medicine · 2022Article
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Abstract
backgroundA T cell-rich tumor microenvironment has been associated with improved clinical outcome and response to immune checkpoint blockade therapies in several adult cancers. Understanding the mechanisms for lack of immune cell infiltration in tumors is critical for expanding immunotherapy efficacy. To gain new insights into the mechanisms of poor tumor immunogenicity, we turned to pediatric cancers, which are generally unresponsive to checkpoint blockade.
methodsRNA sequencing and clinical data were obtained for Wilms tumor, rhabdoid tumor, osteosarcoma, and neuroblastoma from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, and adult cancers from The Cancer Genome Atlas (TCGA). Using an 18-gene tumor inflammation signature (TIS) representing activated CD8
resultsAmong the four pediatric cancers, we observed the lowest TIS scores in Wilms tumor. TIS scores were lower in Wilms tumors compared with matched normal kidney tissues, arguing for loss of endogenous T cell infiltration. Pathway analysis of genes upregulated in Wilms tumor and anti-correlated with TIS revealed activated pathways involved DNA repair. The majority of adult tumors in TCGA also showed high DNA repair scores associated with low TIS. Melanoma samples from an independent cohort revealed an inverse correlation between MSH2
conclusionsIncreased tumor expression of DNA repair genes is associated with a less robust immune response in Wilms tumor and the majority of TCGA tumor types. Surprisingly, the negative relationship between DNA repair score and TIS remained strong across TCGA when correcting for mutation count, indicating a potential role for DNA repair genes outside of preventing the accumulation of mutations. While loss of DNA repair machinery has been associated with carcinogenesis and mutational antigen generation, our results suggest that hyperexpression of DNA repair genes might be prohibitive for antitumor immunity, arguing for pharmacologic targeting of DNA repair as a potential therapeutic strategy.
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