ArticleThe Journal of clinical investigation2021
Breast cancer-derived GM-CSF regulates arginase 1 in myeloid cells to promote an immunosuppressive microenvironment.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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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
75 citing papers in PubMed, 107 citations in OpenAlex.
- Glioma microenvironment: Cellular crosstalk, immunosuppression, and novel therapeutic perspectives.Chinese medical journal · 2026Review
- KMT9 drives T cell exclusion and dysfunction by promoting PMN-MDSCs infiltration and ARG1 expression in prostate cancer.Molecular cancer · 2026Article
- Targeting PID1 generates oxysterols to switch macrophage cell fates for improved antitumor immunity.Nature cancer · 2026Article
- GM-CSF Promotes Neutrophil PD-L1 Expression Through the VEGFR-2/STAT6/CSF2 Signaling Axis in Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineering the tumor immune landscape: Translating non-invasive physical stimulation into tumor-associated macrophage-targeted cancer immunotherapy.Bioengineering & translational medicine · 2026Review
- Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation.Journal of nanobiotechnology · 2026Review
- Interleukin-34-Induced Arg1+ Macrophages Play a Key Role in Breast Cancer Brain Metastasis.Cancer research communications · 2026Article
- CDK4/6 inhibitor ribociclib and doxorubicin combination treatment inhibits breast cancer bone metastasis and enhances T-cell targeted therapy.Journal of bone oncology · 2026Article
- CSF1R inhibitors mitigate CDK4/6 inhibitor-induced immunosuppression to increase antitumor immunity in HR+/HER2- breast cancer.Oncogene · 2026Article
- Understanding the dual role of granulocyte-macrophage colony-stimulating factor in the lung cancer tumor microenvironment and its therapeutic implications.Translational lung cancer research · 2026Review
- Elevated lactate in AML bone marrow contributes to macrophage polarization via GPR81 signaling.Blood advances · 2026Article
- Clinical efficacy and multi-omics analysis of Si-Ni-San for depression treatment in breast cancer patients: a randomized, double-blind, placebo-controlled, crossover trial.Chinese medicine · 2026Article
- Review
- ARG1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting.Frontiers in immunology · 2026Review
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- The double-edged sword of SASP in breast cancer: from tumor suppression to progression and therapy resistance.Frontiers in oncology · 2026Review
- Recent progress in immune evasion mechanisms of triple-negative breast cancer.Journal of translational medicine · 2025Review
- Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer.Breast cancer research : BCR · 2025Article
- Quantitative Analysis of Monocyte-Derived Macrophage NFκB Signaling in Cancer Co-culture Models Using Luciferase-Based Biosensing.Cellular and molecular bioengineering · 2025Article
- Macrophage TBK1 signaling drives the development and outgrowth of breast cancer brain metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (ARG1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular l-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor-derived GM-CSF as the primary regulator of myeloid cell ARG1 expression and local immune suppression through a gene-KO screen of breast tumor cell-produced factors. The induction of myeloid cell ARG1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3 and p38 MAPK and acid signaling through cAMP were required to activate myeloid cell ARG1 expression in a STAT6-independent manner. Importantly, breast tumor cell-derived GM-CSF promoted tumor progression by inhibiting host antitumor immunity, driving a significant accumulation of ARG1-expressing myeloid cells compared with lung and melanoma tumors with minimal GM-CSF expression. Blockade of tumoral GM-CSF enhanced the efficacy of tumor-specific adoptive T cell therapy and immune checkpoint blockade. Taken together, we show that breast tumor cell-derived GM-CSF contributes to the development of the immunosuppressive breast cancer microenvironment by regulating myeloid cell ARG1 expression and can be targeted to enhance breast cancer immunotherapy.
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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.