ArticleCancer immunology research2024
FcγRIIB Is an Immune Checkpoint Limiting the Activity of Treg-Targeting Antibodies in the Tumor Microenvironment.
Article in Cancer immunology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 28 citations in OpenAlex.
- Neoadjuvant Fc-enhanced anti-CTLA-4 targets Tregs to augment androgen deprivation in high-risk prostate cancer: A randomized phase I trial.Cell reports. Medicine · 2026Trial
- Unraveling the Plasma Extracellular Vesicles Proteome: Predictors of Resistance in Immunotherapy of Advanced Melanoma.International journal of cancer · 2026Article
- TLR8 Stimulation Leads to Microenvironment Activation and Enhanced Antibody-Dependent Cellular Responses in CLL.International journal of molecular sciences · 2026Article
- Review
- Regulatory patterns of antibody-dependent cellular phagocytosis-related genes in triple-negative breast cancer: An integrated multi-omics and single-cell analysis.Naunyn-Schmiedeberg's archives of pharmacology · 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
- Precision Fc remodeling via glycosylation-competent CHO display enables ultra-selective FcγRIIIa targeting and enhanced antitumor activity.Journal of biological engineering · 2026Article
- TREM1-PET imaging maps whole-body innate immune responses in a mouse model of metastatic melanoma.Scientific reports · 2026Article
- Role of tumor microenvironment in regulator of tumor progression and immunotherapy.Discover oncology · 2026Review
- Transarterial chemoembolization combined with PD-1 inhibitors for unresectable hepatocellular carcinoma: efficacy and hepatic safety at 4-week versus 6-week treatment intervals.American journal of translational research · 2026Article
- Regulatory T cells in the breast cancer tumor microenvironment: new mechanisms, potential therapeutic strategies and future perspectives.American journal of cancer research · 2026Review
- Preclinical exploration and current clinical applications of immunotherapeutic strategies for hepatocellular carcinoma.Frontiers in immunology · 2026Review
- A low-dose immunotherapy targeting Fc gamma Receptors and heparan sulfate proteoglycan to impact myeloid cells and control cancers with diverse immunosuppressive profiles.Frontiers in immunology · 2026Article
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- IgE based therapeutics are an emerging modality in cancer treatment.Discover oncology · 2025Review
- Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- 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
- Acquired resistance in cancer: towards targeted therapeutic strategies.Nature reviews. Cancer · 2025Review
- Fc-optimized anti-CTLA-4 antibodies increase tumor-associated high endothelial venules and sensitize refractory tumors to PD-1 blockade.Cell reports. Medicine · 2025Article
- A Comprehensive Review of Fc Gamma Receptors and Their Role in Systemic Lupus Erythematosus.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Preclinical murine data indicate that fragment crystallizable (Fc)-dependent depletion of intratumoral regulatory T cells (Treg) is a major mechanism of action of anti-CTLA-4. However, the two main antibodies administered to patients (ipilimumab and tremelimumab) do not recapitulate these effects. Here, we investigate the underlying mechanisms responsible for the limited Treg depletion observed with these therapies. Using an immunocompetent murine model humanized for CTLA-4 and Fcγ receptors (FcγR), we show that ipilimumab and tremelimumab exhibit limited Treg depletion in tumors. Immune profiling of the tumor microenvironment (TME) in both humanized mice and humans revealed high expression of the inhibitory Fc receptor, FcγRIIB, which limits antibody-dependent cellular cytotoxicity/phagocytosis. Blocking FcγRIIB in humanized mice rescued the Treg-depleting capacity and antitumor activity of ipilimumab. Furthermore, Fc engineering of antibodies targeting Treg-associated targets (CTLA-4 or CCR8) to minimize FcγRIIB binding significantly enhanced Treg depletion, resulting in increased antitumor activity across various tumor models. Our results define the inhibitory FcγRIIB as an immune checkpoint limiting antibody-mediated Treg depletion in the TME, and demonstrate Fc engineering as an effective strategy to overcome this limitation and improve the efficacy of Treg-targeting antibodies.
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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 Socratic graph.