ArticleJCI insight2017
β-catenin and PI3Kδ inhibition expands precursor Th17 cells with heightened stemness and antitumor activity.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Wnt/β-Catenin Signaling Pathway Is Involved in Phenotypic Transformation of Human Skin Fibroblasts Induced by IL-17A.Plastic and reconstructive surgery. Global open · 2026Article
- PI3Kδ inhibition alters CD8 T cell differentiation and reprograms the tumor microenvironment following adoptive immunotherapy.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Sorafenib-treated Th9 cells exhibit superior anti-tumor effect in lung metastasis.Scientific reports · 2025Article
- A New Method of Canine CD4International journal of molecular sciences · 2025Article
- Immune cell profiles and predictive modeling in osteoporotic vertebral fractures using XGBoost machine learning algorithms.BioData mining · 2025Article
- Review
- Distinct host preconditioning regimens differentially impact the antitumor potency of adoptively transferred Th17 cells.Journal for immunotherapy of cancer · 2024Article
- Optimization of In Vitro Th17 Polarization for Adoptive Cell Therapy in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2024Article
- Progressively Enhancing Stemness of Adoptively Transferred T Cells with PI3Kδ Blockade Improves Metabolism and Antitumor Immunity.Cancer research · 2024Article
- The role of Th17 cells in chronic lymphocytic leukemia: friend or foe?Blood advances · 2023Review
- Article
- Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment.Nature reviews. Drug discovery · 2022Review
- The effect of Wnt/β-catenin signaling on PD-1/PDL-1 axis in HPV-related cervical cancer.Oncology research · 2022Review
- Targeting the PI3K/Akt/mTOR pathway: A therapeutic strategy in COVID-19 patients.Immunology letters · 2021Review
- Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy.PLoS pathogens · 2021Article
- Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy.Cancers · 2021Review
- PI3K in T Cell Adhesion and Trafficking.Frontiers in immunology · 2021Review
- Fundamentals of T Cell Metabolism and Strategies to Enhance Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Cell composition and expansion strategy can reduce the beneficial effect of AKT-inhibition on functionality of CD8Cancer immunology, immunotherapy : CII · 2020Article
- Ex vivo blockade of PI3K gamma or delta signaling enhances the antitumor potency of adoptively transferred CD8European journal of immunology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
ICOS costimulation generates Th17 cells with durable memory responses to tumor. Herein, we found that ICOS induces PI3K/p110δ/Akt and Wnt/β-catenin pathways in Th17 cells. Coinhibiting PI3Kδ and β-catenin altered the biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed less RORγt, which, in turn, reduced their ability to secrete IL-17. Unexpectedly, these cells were more effective (than uninhibited cells) at regressing tumor when infused into mice, leading to long-term curative responses. PI3Kδ inhibition expanded precursor Th17 cells with a central memory phenotype that expressed nominal regulatory properties (low FoxP3), while β-catenin inhibition enhanced Th17 multifunctionality in vivo. Remarkably, upon TCR restimulation, RORγt and IL-17 rebounded in Th17 cells treated with PI3Kδ and β-catenin inhibitors. Moreover, these cells regained β-catenin, Tcf7, and Akt expression, licensing them to secrete heightened IL-2, persist, and eradicate solid tumors without help from endogenous NK and CD8 T cells. This finding shines a light on ways to repurpose FDA-approved drugs to augment T cell-based cancer immunotherapies.
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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.