ArticleNature communications2024
Targeting IRE1α reprograms the tumor microenvironment and enhances anti-tumor immunity in prostate cancer.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Cancer-associated mitochondrial homeostasis disrupted and retrograde signaling activated.Medical oncology (Northwood, London, England) · 2026Review
- The Unfolded Protein Response as a Modulator of Cancer-Immune Cell Communication in the Tumour Microenvironment.Journal of cellular and molecular medicine · 2026Review
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- p38β-mediated BiP phosphorylation drives stemness and chemoresistance by suppressing UPR activation in hepatocellular carcinoma.Nature communications · 2026Article
- Stress-driven reprogramming of plasmacytoid dendritic cells in intrahepatic cholangiocarcinoma defines a reversible targetable immunosuppressive state.World journal of surgical oncology · 2026Article
- Machine learning-driven development of a novel unfolded protein response-related gene signature for predicting lung adenocarcinoma patient prognosis.BMC cancer · 2026Article
- The mannosyltransferase DPM1 regulates the activity of ER-stress sensor IRE1 in colorectal cancer.Nature communications · 2026Article
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Inhibition of IRE1α kinase increases ferroptosis resistance in triple-negative breast cancer cells.Oncology letters · 2026Article
- Identification and validation of an endoplasmic reticulum stress related model to predict prognosis and tumor microenvironment in neuroblastoma.BMC cancer · 2026Article
- Engineering Multimodal Nanomaterials for Prostate Cancer Theranostics: Design Principles, Recent Advances, and Translational Challenges.International journal of nanomedicine · 2026Review
- Advances in understanding the tumor microenvironment of neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- Single-cell and spatial omics of metabolic-immune ecosystems in prostate cancer: from androgen signaling to therapy resistance.Frontiers in immunology · 2026Review
- Multi-omics analyses related to unfolded protein response in prostate cancer implicate pro-tumor role of IFRD1.Frontiers in immunology · 2026Article
- Targeting the unfolded protein response in cancer: mechanisms, small-molecule inhibitors, and translational challenges.Frontiers in immunology · 2026Review
- Combined assessment of ERO1A expression and CD163Frontiers in oncology · 2026Article
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.Cancer biology & therapy · 2025Article
- The Unfolded Protein Response-Novel Mechanisms, Challenges, and Key Considerations for Therapeutic Intervention.Cancers · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Unfolded protein response (UPR) is a central stress response pathway that is hijacked by tumor cells for their survival. Here, we find that IRE1α signaling, one of the canonical UPR arms, is increased in prostate cancer (PCa) patient tumors. Genetic or small molecule inhibition of IRE1α in syngeneic mouse PCa models and an orthotopic model decreases tumor growth. IRE1α ablation in cancer cells potentiates interferon responses and activates immune system related pathways in the tumor microenvironment (TME). Single-cell RNA-sequencing analysis reveals that targeting IRE1α in cancer cells reduces tumor-associated macrophage abundance. Consistently, the small molecule IRE1α inhibitor MKC8866, currently in clinical trials, reprograms the TME and enhances anti-PD-1 therapy. Our findings show that IRE1α signaling not only promotes cancer cell growth and survival but also interferes with anti-tumor immunity in the TME. Thus, targeting IRE1α can be a promising approach for improving anti-PD-1 immunotherapy in PCa.
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Registered trials
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.