ArticleScience immunology2019
GCN2 drives macrophage and MDSC function and immunosuppression in the tumor microenvironment.
Article in Science immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 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
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
- Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation.Current oncology (Toronto, Ont.) · 2022Pooled it
- The integrated stress response kinase GCN2 prevents ZAKα-Dependent inflammatory hyperactivation in macrophages.The Journal of biological chemistry · 2026Article
- Metabolic-epigenetic crosstalk in innate immune cell plasticity within the tumor microenvironment.Experimental & molecular medicine · 2026Review
- Immunometabolic Stress and Immune Suppression in Clear-Cell Renal Cell Carcinoma: Perspectives in Therapeutic Strategy.International journal of molecular sciences · 2026Review
- Myeloid-Derived Suppressor Cells in Cancer: Metabolic Reprogramming, Immune Crosstalk, and Therapeutic Targeting.Cancers · 2026Review
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Nano-granulated zoledronate sensitizes innate immune metabolism to enhance vaccine-induced and antitumor immunity.Cell reports. Medicine · 2026Article
- Metabolic and transcriptional plasticity supports CD8Immunity · 2026Article
- Elevated GCN2 levels in cancer cells confer protection from mitotic stress and faster cell movement.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- The remarkable legacy of the K6/ODC mouse: mechanisms of polyamine-promoted tumorigenesis revealed.Amino acids · 2026Review
- Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases.Ageing research reviews · 2026Review
- LDLRJournal of clinical and translational hepatology · 2026Article
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- Short-chain fatty acids in the tumor microenvironment: from molecular mechanisms to cancer therapy.Theranostics · 2026Review
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
Abstract
General control nonderepressible 2 (GCN2) is an environmental sensor controlling transcription and translation in response to nutrient availability. Although GCN2 is a putative therapeutic target for immuno-oncology, its role in shaping the immune response to tumors is poorly understood. Here, we used mass cytometry, transcriptomics, and transcription factor-binding analysis to determine the functional impact of GCN2 on the myeloid phenotype and immune responses in melanoma. We found that myeloid-lineage deletion of GCN2 drives a shift in the phenotype of tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs) that promotes antitumor immunity. Time-of-flight mass cytometry (CyTOF) and single-cell RNA sequencing showed that this was due to changes in the immune microenvironment with increased proinflammatory activation of macrophages and MDSCs and interferon-γ expression in intratumoral CD8
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What OpenQuestion holds
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.