ArticleCell reports2021
Pharmacological Wnt ligand inhibition overcomes key tumor-mediated resistance pathways to anti-PD-1 immunotherapy.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06513624 (A Phase 1B Investigator Initiated Study To Evaluate The Preliminary Activity, Safety And Tolerability Of ETC-159 In Combination With Pembrolizumab In Advanced MSS/pMMR Ovarian Cancers.), which is not on this map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1B Investigator Initiated Study To Evaluate The Preliminary Activity, Safety And Tolerability Of ETC-159 In Combination With Pembrolizumab In Advanced MSS/pMMR Ovarian Cancers.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Transcriptomic datasets of cancer patients treated with immune-checkpoint inhibitors: a systematic review.Journal of translational medicine · 2022Pooled it
- Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.Genes & diseases · 2027Review
- Engineering bispecific exosome activators of T cells to target immune checkpoint inhibitor-resistant metastatic melanoma.Nature biotechnology · 2026Article
- Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.Carcinogenesis · 2026Review
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- IDO family: the metabolic crossroads connecting immunity, nerves and tumors.Journal of translational medicine · 2026Review
- PRECOG update: an augmented resource of clinical outcome associations with gene expression for adult, pediatric, and immunotherapy cohorts.Nucleic acids research · 2026Article
- Comprehensive bioinformatics analysis reveals prognostic significance and immunological roles of WNT gene family in breast cancer.Scientific reports · 2025Article
- Favorable response to nivolumab combined with radiotherapy for retroperitoneal leiomyosarcoma.International cancer conference journal · 2025Article
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- GLI2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating WNT and Prostaglandin Signaling.Cancer research · 2025Article
- Elevated KIF2C Expression Drives Osteosarcoma Progression by Modulating the Wnt/β-Catenin Signaling Pathway and Contributing to an Immunosuppressive Tumor Microenvironment.Cancer medicine · 2025Article
- Function of antigen-presenting cells in non-small-cell lung cancer (NSCLC).Medical oncology (Northwood, London, England) · 2025Review
- Review
- Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation.Molecular cancer · 2025Review
- WNT11 Promotes immune evasion and resistance to Anti-PD-1 therapy in liver metastasis.Nature communications · 2025Article
- Signature Construction Associated with Tumor-Infiltrating Macrophages Identifies IRF8 as a Novel Biomarker for Immunotherapy in Advanced Gastric Cancer.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
While immune checkpoint blockade is associated with prolonged responses in multiple cancers, most patients still do not benefit from this therapeutic strategy. The Wnt-β-catenin pathway is associated with diminished T cell infiltration; however, activating mutations are rare, implicating a role for autocrine/paracrine Wnt ligand-driven signaling in immune evasion. In this study, we show that proximal mediators of the Wnt signaling pathway are associated with anti-PD-1 resistance, and pharmacologic inhibition of Wnt ligand signaling supports anti-PD-1 efficacy by reversing dendritic cell tolerization and the recruitment of granulocytic myeloid-derived suppressor cells in autochthonous tumor models. We further demonstrate that the inhibition of Wnt signaling promotes the development of a tumor microenvironment that is more conducive to favorable responses to checkpoint blockade in cancer patients. These findings support a rationale for Wnt ligand-focused treatment approaches in future immunotherapy clinical trials and suggest a strategy for selecting those tumors more responsive to Wnt inhibition.
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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.