Evidence map›Paper›PMID 34433055›Full record

ArticleCell reports2021

Antibody:CD47 ratio regulates macrophage phagocytosis through competitive receptor phosphorylation.

Emily C Suter, Eva M Schmid, Andrew R Harris, Erik Voets, Brian Francica, Daniel A Fletcher

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Review
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  4. Review
  5. Functional Differences Between SIRPα Splice Isoforms.Genes to cells : devoted to molecular & cellular mechanisms · 2025
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  6. Review
  7. Clustered macrophages cooperate to eliminate tumors via coordinated intrudopodia.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Article
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  10. Review
  11. Article
  12. Microrobotic Swarms for Cancer Therapy.Research (Washington, D.C.) · 2025
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 2 countries.

Emily C SuterDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA, USA; UC Berkeley/UC San Francisco Graduate Group in Bioengineering, Berkeley, CA, USA.
Eva M SchmidDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Andrew R HarrisDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA, USA; Department of Mechanical and Aerospace Engineering, Carleton University, Ottawa, ON, Canada.
Erik VoetsAduro Biotech Europe, Oss, the Netherlands.
Brian FrancicaAduro Biotech Inc., Emeryville, CA, USA.
Daniel A FletcherDepartment of Bioengineering, University of California, Berkeley, Berkeley, CA, USA; UC Berkeley/UC San Francisco Graduate Group in Bioengineering, Berkeley, CA, USA; Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. Electronic address: fletch@berkeley.edu.
Aduro BioTech (United States) · USCarleton University · CALawrence Berkeley National Laboratory · USUniversity of California, Berkeley · USUniversity of California, San Francisco · US

Funding

Mechanical Regulation of Actin Binding ProteinsR01GM134137 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI FLETCHER, DANIEL A · 2019 to 2022
$1.5M
NIGMS NIH HHS R01 GM134137
6 · The paper itself

Abstract

Cancer immunotherapies often modulate macrophage effector function by introducing either targeting antibodies that activate Fcγ receptors (FcγRs) or blocking antibodies that disrupt inhibitory SIRPα-CD47 engagement. However, how these competing signals are integrated is poorly understood, raising questions about how to effectively titrate immune responses. Here, we find that macrophage phagocytic decisions are regulated by the ratio of activating ligand to inhibitory ligand over a broad range of absolute molecular densities. Using both endogenous and chimeric receptors, we show that activating:inhibitory ligand ratios of at least 10:1 are required to promote phagocytosis of model antibody-opsonized CD47-inhibited targets and that lowering that ratio reduces FcγR phosphorylation because of inhibitory phosphatases recruited to CD47-bound SIRPα. We demonstrate that ratiometric signaling is critical for phagocytosis of tumor cells and can be modified by blocking SIRPα, indicating that balancing targeting and blocking antibodies may be important for controlling macrophage phagocytosis in cancer immunotherapy.

Indexed as

AnimalsAntibodiesAntibodies, BlockingCarrier ProteinsCD47 AntigenNeoplasmsPhagocytosisPhosphorylationReceptors, IgGAntibodiesAntibodies, BlockingCarrier ProteinsCD47 AntigenReceptors, IgGcancer immunotherapyCD47checkpoint blockadeFc receptorITAMITIMmacrophagephagocytosisSIRPαtherapeutic antibody

Identifiers

PMID34433055
PMCPMC8477956
OpenAlexW3194520351

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.