ArticleMedComm2023
Thymol targeting interleukin 4 induced 1 expression reshapes the immune microenvironment to sensitize the immunotherapy in lung adenocarcinoma.
Article in MedComm, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- Topology-Based Biomarkers Accurately Predict Breast Cancer Outcome and Survival.Cancer research · 2026Article
- Phytochemistry and Bioactivities of Thymol and Carvacrol: Molecular Pathways, Metabolism, and Therapeutic Insights.Food science & nutrition · 2026Review
- IL4I1⁺ Macrophages and TDO2⁺ Myofibroblasts Drive AhR-Mediated Immunosuppression and Ferroptosis Resistance in Solid Predominant Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Thymol: properties, synthesis, mechanism of action, and applications.Frontiers in nutrition · 2026Review
- Pathological significance and therapeutic prospects ofCell adhesion & migration · 2025Article
- Article
- Multi-omics profiling reveals PLEKHA6 as a modulator of β-catenin signaling and therapeutic vulnerability in lung adenocarcinoma.American journal of cancer research · 2025Article
- Thymol as adjuvant in oncology: molecular mechanisms, therapeutic potentials, and prospects for integration in cancer management.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Article
- Targeting amino acid-metabolizing enzymes for cancer immunotherapy.Frontiers in immunology · 2024Review
- IL4I1: a novel molecular biomarker represents an inflamed tumor microenvironment and precisely predicts the molecular subtype and immunotherapy response of bladder cancer.Frontiers in pharmacology · 2024Article
- Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint blockades are the most promising therapy in lung adenocarcinoma (LUAD). However, the response rate remains limited, underscoring the urgent need for effective sensitizers. Interleukin 4 induced 1 (IL4I1) is reported to have immunoinhibitory and tumor-promoting effects in several cancers. However, the targetable value of IL4I1 in sensitizing the immunotherapy is not clear, and there is a lack of effective small molecules that specifically target IL4I1. Here, we show that silencing IL4I1 significantly remodels the immune microenvironment via inhibiting aryl hydrocarbon receptor (AHR) signaling, thereby enhancing the efficacy of anti-PD-1 antibody in LUAD, which suggests that IL4I1 is a potential drug target for the combination immunotherapy. We then identify thymol as the first small molecule targeting IL4I1 transcription through a drug screening. Thymol inhibits the IL4I1 expression and blocks AHR signaling in LUAD cells. Thymol treatment restores the antitumor immune response and suppresses the progression of LUAD in an orthotopic mouse model. Strikingly, the combination treatment of thymol with anti-PD-1 antibody shows significant tumor regression in LUAD mice. Thus, we demonstrate that thymol is an effective small molecule to sensitize the PD-1 blockade in LUAD via targeting IL4I1, which provides a novel strategy for the immunotherapy of LUAD.
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