ArticleCell death & disease2024
IL-4/IL-4R axis signaling drives resistance to immunotherapy by inducing the upregulation of Fcγ receptor IIB in M2 macrophages.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Chronic Stress Promotes Gastric Cancer Metastasis by Inducing Microbiota-Associated Kynurenine Accumulation and Macrophage Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- cGAS-STING pathway modulation: A new hope for neural regeneration.Neural regeneration research · 2026Article
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- Activating an interleukin 4-FLT3-STAT6 axis in multipotent progenitors restores lymphopoiesis in inflammation and aging.Immunity · 2026Article
- Cytokine Networks Reprogramming the Osteo-Immune Microenvironment in Cancer Bone Metastasis.Calcified tissue international · 2026Review
- Ferroptosis in prostatitis: pathogenic mechanisms and therapeutic advances.Molecular and cellular biochemistry · 2026Review
- Microfluidic Biofabrication of a Hydrogel Vessel-Like Structure for Interrogating Tumor Cell Propagation in a Breast Cancer-on-a-Chip Model.Advanced healthcare materials · 2026Article
- Subcutaneous immunotherapy-induced IgG1 suppresses allergic airway inflammation through FcγRIIb-mediated inhibition of group 2 innate lymphoid cell proliferation.The World Allergy Organization journal · 2026Article
- CD90 mediates gastric cancer immune evasion though regulating IGF2BP2 to stabilize the m6A-CD47/SIRPα axis.Cancer cell international · 2026Article
- The impact of neoadjuvant chemoimmunotherapy on pulmonary function in non-small cell lung cancer patients.Translational lung cancer research · 2026Article
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- Role of histone modifications in gastric cancer (Review).International journal of oncology · 2026Review
- BCG-trained macrophages promote pan-anti-tumor activity through epigenetic rewiring of NOX2-ROS axis.Journal of experimental & clinical cancer research : CR · 2026Article
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Research progress on the correlation between OPN and immune escape of gastric cancer.Clinical and experimental medicine · 2026Review
- Macrophage polarization in hematologic cancers: mechanisms and therapeutic strategies.Blood research · 2026Review
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- The Pleiotropic Roles of Cytokines in Chimeric Antigen Receptor T-cell Therapy.Cancer immunology research · 2026Review
- Molecular innate immune programs of tumor-associated macrophages in immune checkpoint blockade resistance: a staged framework from suppressive circuitry to translational bottlenecks.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
In recent years, immunotherapy, particularly PD-1 antibodies, have significantly enhanced the outcome of gastric cancer patients. Despite these advances, some patients do not respond well to treatment, highlighting the need to understand resistance mechanisms and develop predictive markers of treatment effectiveness. This study retrospectively analyzed data from 106 patients with stage IV gastric cancer who were treated with first-line immunotherapy in combination with chemotherapy. By comparing plasma cytokine levels between patients resistant and sensitive to PD-1 antibody therapy, the researchers identified elevated IL-4 expression in the resistant patients. Mechanical investigations revealed that IL-4 induces metabolic changes in macrophages that activate the PI3K/AKT/mTOR pathway. This alteration promotes ATP production, enhances glycolysis, increases lactic acid production, and upregulates FcγRIIB expression in macrophages. Ultimately, these changes lead to CD8+ T cell dysfunction and resistance to PD-1 antibody therapy in gastric cancer. These findings highlight the role of IL-4-induced macrophage polarization and metabolic reprogramming in immune resistance and verify IL-4 as potential targets for improving treatment outcomes in gastric cancer patients.
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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.