ArticleThe Journal of clinical investigation2023
IL-1 receptor-associated kinase-3 acts as an immune checkpoint in myeloid cells to limit cancer immunotherapy.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- ADAMDEC1 predicts prognosis and immunotherapy response in a pan-cancer study with experimental validation.Discover oncology · 2026Article
- Single-cell and spatial transcriptomics reveal that the CXCL12-CXCR4 axis drives the immune-desert phenotype in small cell lung cancer by recruiting immunosuppressive CXCR4Journal for immunotherapy of cancer · 2026Article
- Genome-wide CRISPR screens in primary human natural killer cells identify countermeasures against immunosuppressive environment.Nature communications · 2026Article
- The cost of persistent alarm: temporal transcriptional reprogramming of macrophages from acute activation to chronic immune suppression by day 11.Frontiers in immunology · 2026Article
- Integrated analysis of bioinformatics, mendelian randomization, and experimental validation reveals novel diagnostic and therapeutic targets for osteoarthritis: progesterone as a potential therapeutic agent.Journal of orthopaedic surgery and research · 2025Article
- Exploring the biological functions and immune regulatory roles of IRAK3, TNFRSF1A, CX3CR1, and JUNB in T2DM combined with MAFLD: integrated bioinformatics and single-cell analysis.Frontiers in immunology · 2025Article
- IRAK3 is upregulated in rheumatoid arthritis synovium and delays the onset of experimental arthritis.Frontiers in immunology · 2025Article
- Integrative analysis of single-cell and microarray data reveals SPI1-centered macrophage regulatory signatures in ulcerative colitis.Frontiers in genetics · 2025Article
- Evaluation of effectiveness of bacteriophage purification methods.Virology journal · 2024Article
- IL-1 receptor-associated kinase 3 (IRAK3) in lung adenocarcinoma predicts prognosis and immunotherapy resistance: involvement of multiple inflammation-related pathways.Translational lung cancer research · 2024Article
- Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma.The Journal of clinical investigation · 2024Article
- IL-1 Family Members in Bone Sarcomas.Cells · 2024Review
- LRP11 promotes stem-like T cells via MAPK13-mediated TCF1 phosphorylation, enhancing anti-PD1 immunotherapy.Journal for immunotherapy of cancer · 2024Article
- Serum IRAK3 may serve as a prognostic biomarker in acute supratentorial intracerebral hemorrhage: findings from a prospective observational cohort study.Frontiers in neurology · 2024Article
- Tumor-associated neutrophils upregulate PANoptosis to foster an immunosuppressive microenvironment of non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Whole-Genome Resequencing Reveals Selection Signatures of Abigar Cattle for Local Adaptation.Animals : an open access journal from MDPI · 2023Article
- Mutations in the Vicinity of the IRAK3 Guanylate Cyclase Center Impact Its Subcellular Localization and Ability to Modulate Inflammatory Signaling in Immortalized Cell Lines.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammatory mediators released by cancer cells promote the induction of immune suppression and tolerance in myeloid cells. IL-1 receptor-associated kinase-3 (IRAK3) is a pseudokinase that inhibits IL-1/TLR signaling, but its role in patients treated with immune checkpoint blockade (ICB) therapy remains unclear. Using RNA-Seq data from the IMvigor210 trial, we found that tumors with high IRAK3 expressions showed enriched antiinflammatory pathways and worse clinical response to ICB therapy. Upon IRAK3 protein deletion with CRISPR/Cas9, primary human monocytes displayed altered global protein expression and phosphorylation in quantitative proteomics and released more proinflammatory cytokines in response to stimulation. Bone marrow-derived macrophages from an IRAK3 CRISPR KO mouse model demonstrated a proinflammatory phenotype and enhanced sensitivity to TLR agonists compared with WT cells. IRAK3 deficiency delayed the growth of carcinogen-induced and oncogene-driven murine cancer cells and induced enhanced activation in myeloid cells and T cells. Upon ICB treatment, IRAK3-KO mice showed enrichment of TCF1+PD-1+ stem-like memory CD8+ T cells and resulted in superior growth inhibition of immunologically cold tumors in vivo. Altogether, our study demonstrated what we believe to be a novel cancer-driven immune tolerance program controlled by IRAK3 in humans and mice and proposed its suitability as an immunotherapy target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.