ArticleCancer science2022
Glutamate blunts cell-killing effects of neutrophils in tumor microenvironment.
Article in Cancer science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses 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
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Prognostic significance of pretreatment systemic immune-inflammation index (SII) in patients with cervical cancer: a meta-analysis.World journal of surgical oncology · 2025Pooled it
- Prognostic value of the pretreatment systemic immune-inflammation index in patients with prostate cancer: a systematic review and meta-analysis.Journal of translational medicine · 2023Pooled it
- Neuro-immune crosstalk in lung cancer brain metastasis: mechanisms, therapeutic targets, and translational opportunities.Medical oncology (Northwood, London, England) · 2026Review
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- Review
- Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Decoding mitochondrial signaling: neutrophil-tumor cell crosstalk in orchestrating cancer progression.Journal of translational medicine · 2026Review
- The neural niche in cancer: mechanistic insights into tumor-neuron-immune crosstalk and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Metabolic licensing and restriction of innate immunity in the tumor microenvironment.Frontiers in immunology · 2026Review
- Metabolic Control of Immunity-Unveiling Neutrophil Mechanisms.Advances in experimental medicine and biology · 2026Review
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Prognostic value of systemic inflammation response index in cervical cancer: a meta-analysis.Future science OA · 2025Review
- Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Decoding the metabolic dialogue in the tumor microenvironment: from immune suppression to precision cancer therapies.Experimental hematology & oncology · 2025Review
- Article
- Abnormal changes in metabolites caused by mJournal of advanced research · 2025Review
- Association between systemic immune-inflammation index and the risk of all-cause, cancer and non-cancer mortality in the general population: results from national health and nutrition examination survey 2005-2018.BMC public health · 2025Article
- Metabolic reprogramming of tumor-associated neutrophils in tumor treatment and therapeutic resistance.Frontiers in cell and developmental biology · 2025Review
- Effect of neutrophils on tumor immunity and immunotherapy resistance with underlying mechanisms.Cancer communications (London, England) · 2025Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Neutrophils are the first defenders of the innate system for injury and infection. They have gradually been recognized as important participants in tumor initiation and development due to their heterogeneity and plasticity. In the tumor microenvironment (TME), neutrophils can exert antitumor and protumor functions, depending on the surroundings. Tumor cells systemically alter intracellular amino acid (AA) metabolism and extracellular AA distribution to meet their proliferation need, leading to metabolic reprogramming and TME reshaping. However, the underlying mechanisms that determine how altered AAs affect neutrophils in TME are less-explored. Here, we identified that abundant glutamate releasing from tumor cells blunted neutrophils' cell-killing effects toward tumor cells in vitro and in vivo. Mass spectrometric detection, flow cytometry, and western blot experiments proved that increased levels of pSTAT3/RAB10/ARF4, mediated by glutamate, were accompanied with immunosuppressive phenotypes of neutrophils in TME. We also discovered that riluzole, an FDA-approved glutamate release inhibitor, significantly inhibited tumor growth by restoring neutrophils' cell-killing effects and decreasing glutamate secretion from tumor cells. These findings highlight the importance of tumor-released glutamate on neutrophil transformation in TME, providing new possible cancer treatments targeting altered glutamate metabolism.
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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.