Evidence map›Paper›PMID 36169352›Full record

ArticleACS synthetic biology2022

Induced CD45 Proximity Potentiates Natural Killer Cell Receptor Antagonism.

Junming Ren, Yeara Jo, Lora K Picton, Leon L Su, David H Raulet, K Christopher Garcia

Open access · hybridAbstract read
In one paragraph

Article in ACS synthetic biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

16 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Specific Biomarkers Involved in Sarcoidosis Diagnosis and Prognosis.International journal of molecular sciences · 2026
    Article
  3. Review
  4. Precise Regulation of Membrane Proteins: From Physical Technology to Biomolecular Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  5. Article
  6. Adenoviral E3/49K: CD45-targeted immune evasion and therapeutic potential.Frontiers in cellular and infection microbiology · 2026
    Review
  7. Article
  8. Article
  9. Induced proximity at the cell surface.Nature biotechnology · 2025
    Review
  10. Article
  11. The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Two in one: the emerging concept of bifunctional antibodies.Current opinion in biotechnology · 2024
    Review
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 2 institutions in 1 country.

Junming RenDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, United States.ORCID 0000-0002-0764-0882
Yeara JoDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, United States.
Lora K PictonDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, United States.
Leon L SuDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, United States.
David H RauletDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, United States.ORCID 0000-0002-1257-8649
K Christopher GarciaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, United States.ORCID 0000-0001-9273-0278
Howard Hughes Medical Institute · USUniversity of California, Berkeley · US

Funding

STING-dependent activation of Natural Killer cells by viral and tumor DNAR01AI113041 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI RAULET, DAVID H · 2014 to 2024
$4.1M
Strategies for Receptor inhibition in immunotherapyR01CA177684 · NCI · STANFORD UNIVERSITY · PI DOUGAN, MICHAEL LAWRENCE, GARCIA, KENAN CHRISTOPHER · 2014 to 2025
$3.5M
Mechanisms underlying combination therapy mobilizing NK cellsR01CA270790 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI DAVID H RAULET · 2022 to 2026
$2.3M
NCI NIH HHS R01 CA177684NCI NIH HHS R01 CA270790NIAID NIH HHS R01 AI113041
6 · The paper itself

Abstract

Natural killer (NK) cells are a major subset of innate immune cells that are essential for host defense against pathogens and cancer. Two main classes of inhibitory NK receptors (NKR), KIR and CD94/NKG2A, play a key role in suppressing NK activity upon engagement with tumor cells or virus-infected cells, limiting their antitumor and antiviral activities. Here, we find that single-chain NKR antagonists linked to a VHH that binds the cell surface phosphatase CD45 potentiate NK and T activities to a greater extent than NKR blocking antibodies alone in vitro. We also uncovered crosstalk between NKG2A and Ly49 that collectively inhibit NK cell activation, such that CD45-NKG2A and CD45-Ly49 bispecific molecules show synergistic effects in their ability to enhance NK cell activation. The basis of the activity enhancement by CD45 ligation may reflect greater antagonism of inhibitory signaling from engagement of MHC I on target cells, combined with other mechanisms, including avidity effects, tonic signaling, antagonism of weak inhibition from engagement of MHC I on non-target cells, and possible CD45 segregation within the NK cell-target cell synapse. These results uncover a strategy for enhancing the activity of NK and T cells that may improve cancer immunotherapies.

Indexed as

NK Cell Lectin-Like Receptor Subfamily CReceptors, ImmunologicAntibodies, BlockingAntigens, CDAntiviral AgentsReceptors, Natural Killer CellAntibodies, BlockingAntigens, CDAntiviral AgentsNK Cell Lectin-Like Receptor Subfamily CReceptors, ImmunologicReceptors, Natural Killer Cellbispecific antibodiesCD45induced proximitynatural killer cell receptorsprotein engineering

Identifiers

PMID36169352
PMCPMC9594326
OpenAlexW4297460510

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.