ArticleBlood2020
Macrophage hypophagia as a mechanism of innate immune exhaustion in mAb-induced cell clearance.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- Acalabrutinib and high-frequency low-dose subcutaneous rituximab for initial therapy of chronic lymphocytic leukemia.Blood advances · 2023Trial
- Clinical and inflammatory factors associated with prevalent gout in a Brazilian hospital population.Clinics (Sao Paulo, Brazil) · 2026Article
- Efficacy of high-frequency low-dose rituximab and acalabrutinib in chronic lymphocytic leukemia.HemaSphere · 2026Article
- SIRPα ablated iPSC-derived macrophages resist hypophagia and enhance mAb-dependent and CAR-mediated cytotoxicity of solid tumors.Molecular therapy. Oncology · 2026Article
- Lymph node microenvironment remodeling unlocks local antibody-mediated B cell depletion.Science advances · 2026Article
- Molecular mechanisms behind the temporal dynamics of LPS-induced inflammatory response in splenic phagocytes of the wall lizard Hemidactylus flaviviridis.The Journal of experimental biology · 2026Article
- Hyperactive Rac converts sublethal to lethal trogocytosis in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting phagocytosis checkpoints for cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Remodeling of Cardiac Macrophage Subsets Serves as a Critical Driver of Early Diabetic Myocardial Injury.Journal of inflammation research · 2026Article
- Complement-mediated ADCP as a distinct and finite cytotoxic mechanism of monoclonal antibodies.Frontiers in immunology · 2026Article
- Hyperactive Rac converts sublethal nibbling to lethal phagocytosisbioRxiv : the preprint server for biology · 2025Article
- Mitochondrial dysfunction in myeloid cells: a central deficit in autoimmune diseases.Trends in immunology · 2025Review
- Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large B-cell lymphomas and regulates the pro-tumor microenvironment.Haematologica · 2025Article
- The Benefits and Safety of Monoclonal Antibodies: Implications for Cancer Immunotherapy.Journal of inflammation research · 2025Review
- Biochemical and biophysical mechanisms macrophages use to tune phagocytic appetite.Journal of cell science · 2025Review
- Phosphoproteomic Profiling Reveals mTOR Signaling in Sustaining Macrophage Phagocytosis of Cancer Cells.Cancers · 2024Article
- The senescence-associated secretory phenotype and its physiological and pathological implications.Nature reviews. Molecular cell biology · 2024Review
- A Novel Engineering Cell Therapy Platform Mimicking the Immune Thrombocytopenia-Derived Platelets to Inhibit Cytokine Storm in Hemophagocytic Lymphohistiocytosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Prior Fc receptor activation primes macrophages for increased sensitivity to IgG via long-term and short-term mechanisms.Developmental cell · 2024Article
- Antibody-mediated phagocytosis in cancer immunotherapy.Immunological reviews · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophage antibody (Ab)-dependent cellular phagocytosis (ADCP) is a major cytotoxic mechanism for both therapeutic unconjugated monoclonal Abs (mAbs) such as rituximab and Ab-induced hemolytic anemia and immune thrombocytopenia. Here, we studied the mechanisms controlling the rate and capacity of macrophages to carry out ADCP in settings of high target/effector cell ratios, such as those seen in patients with circulating tumor burden in leukemic phase disease. Using quantitative live-cell imaging of primary human and mouse macrophages, we found that, upon initial challenge with mAb-opsonized lymphocytes, macrophages underwent a brief burst (<1 hour) of rapid phagocytosis, which was then invariably followed by a sharp reduction in phagocytic activity that could persist for days. This previously unknown refractory period of ADCP, or hypophagia, was observed in all macrophage, mAb, and target cell conditions tested in vitro and was also seen in vivo in Kupffer cells from mice induced to undergo successive rounds of αCD20 mAb-dependent clearance of circulating B cells. Importantly, hypophagia had no effect on Ab-independent phagocytosis and did not alter macrophage viability. In mechanistic studies, we found that the rapid loss of activating Fc receptors from the surface and their subsequent proteolytic degradation were the primary mechanisms responsible for the loss of ADCP activity in hypophagia. These data suggest hypophagia is a critical limiting step in macrophage-mediated clearance of cells via ADCP, and understanding such limitations to innate immune system cytotoxic capacity will aid in the development of mAb regimens that could optimize ADCP and improve patient outcome.
Indexed as
Identifiers
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.