ArticleJournal of experimental & clinical cancer research : CR2022
HIF activation enhances FcγRIIb expression on mononuclear phagocytes impeding tumor targeting antibody immunotherapy.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 28 citations in OpenAlex.
- Tailored FcγR blockade enhances immune checkpoint therapy and overcomes resistance.Journal of experimental & clinical cancer research : CR · 2026Article
- The HCG11/QKI5 Axis Regulates Endothelial Angiogenic Adaptation During Chronic Cerebral Hypoperfusion.CNS neuroscience & therapeutics · 2026Article
- Tumor-Derived Exosomes Deliver Membrane-Bound Fgl2 to Activate FcγRIIB-Mediated Immunosuppression in Myeloid-Derived Suppressor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unmasking FCGR2B as a high-grade serous ovarian cancer specific marker of immune suppression and tumor progression through multi-omics mining.Translational oncology · 2026Article
- Understanding Immune Cell Adaptation to Tumor Hypoxia for Maximized Therapeutic Efficacy of Immunotherapy: Biology and Non-invasive Imaging Application.Cancer research and treatment · 2026Review
- A "Function-First" Approach to Identify Regulatory T cell-Targeting Antibodies for Immunotherapy.Cancer immunology research · 2025Article
- A First-in-Class mAb (BI-1607) Targeting FcγRIIB: Preclinical Data and First-in-Human Studies in Patients with HER2-Positive Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The ETS-family transcription factor PU.1 is a critical regulator of the inhibitory Fcγ receptor IIB expression in humans.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Constructing a tumor immune microenvironment-driven prognostic model in acute myeloid leukemia using bioinformatics and validation data.Scientific reports · 2025Article
- Comparison of human macrophages derived from peripheral blood and bone marrow.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia.Nature reviews. Immunology · 2025Review
- Long-term adaptation of lymphoma cell lines to hypoxia is mediated by diverse molecular mechanisms that are targetable with specific inhibitors.Cell death discovery · 2025Article
- A critical guideline for controlling monocyte-derived macrophages phenotypes.Frontiers in immunology · 2025Review
- Therapeutic targeting of tumour-associated macrophage receptors.Immunotherapy advances · 2025Review
- Key Genes Associated With Functional Specialization of Neonatal Peripheral Monocytes.Human mutation · 2025Article
- Developing a 3D bone model of osteosarcoma to investigate cancer mechanisms and evaluate treatments.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations.Journal for immunotherapy of cancer · 2024Article
- Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- FcγRIIB Is an Immune Checkpoint Limiting the Activity of Treg-Targeting Antibodies in the Tumor Microenvironment.Cancer immunology research · 2024Article
- Fcγ receptors and immunomodulatory antibodies in cancer.Nature reviews. Cancer · 2024Review
Corrections and comments
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Authors and funding
31 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHypoxia is a hallmark of the tumor microenvironment (TME) and in addition to altering metabolism in cancer cells, it transforms tumor-associated stromal cells. Within the tumor stromal cell compartment, tumor-associated macrophages (TAMs) provide potent pro-tumoral support. However, TAMs can also be harnessed to destroy tumor cells by monoclonal antibody (mAb) immunotherapy, through antibody dependent cellular phagocytosis (ADCP). This is mediated via antibody-binding activating Fc gamma receptors (FcγR) and impaired by the single inhibitory FcγR, FcγRIIb.
methodsWe applied a multi-OMIC approach coupled with in vitro functional assays and murine tumor models to assess the effects of hypoxia inducible factor (HIF) activation on mAb mediated depletion of human and murine cancer cells. For mechanistic assessments, siRNA-mediated gene silencing, Western blotting and chromatin immune precipitation were utilized to assess the impact of identified regulators on FCGR2B gene transcription.
resultsWe report that TAMs are FcγRIIb
conclusionOur findings provide a detailed molecular and cellular basis for hypoxia driven resistance to antitumor mAb immunotherapy, unveiling a hitherto unexplored aspect of the TME. These findings provide a mechanistic rationale for the modulation of FcγRIIb expression or its blockade as a promising strategy to enhance approved and novel mAb immunotherapies.
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What Socratic 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 Socratic graph.