Evidence map›Paper›PMID 30902904›Full record

ArticleScience immunology2019

Interfacial actin protrusions mechanically enhance killing by cytotoxic T cells.

Fella Tamzalit, Mitchell S Wang, Weiyang Jin, Maria Tello-Lafoz, Vitaly Boyko, John M Heddleston, Charles T Black, Lance C Kam, Morgan Huse

Open access · greenAbstract read
In one paragraph

Article in Science immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
8.9field-weighted citation impact, top 1% 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

79 citing papers in PubMed, 130 citations in OpenAlex.

  1. Article
  2. Article
  3. Viscoelastic Niches Shape γδ T-Cell Phenotype and Effector Function.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025
    Review
  13. Review
  14. Article
  15. Dynamic Plasma Membrane Topography Linked With Arp2/3 Actin Network Induction During Cell Shape Change.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  16. Review
  17. Review
  18. Article
  19. Bottom-up synthetic immunology.Nature nanotechnology · 2024
    Review
  20. Article

19 more citing papers are in PubMed but not listed here.

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

9 authors at 5 institutions in 1 country.

Fella TamzalitImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-8155-1098
Mitchell S WangPharmacology Graduate Program, Weill Cornell Medical College, New York, NY, USA.ORCID 0000-0002-6851-3596
Weiyang JinDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID 0000-0001-8206-1234
Maria Tello-LafozImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-8909-6800
Vitaly BoykoMolecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
John M HeddlestonAdvanced Imaging Center, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.ORCID 0000-0002-9289-4114
Charles T BlackCenter for Functional Nanomaterials, Brookhaven National Laboratory, Upton, NY, USA.ORCID 0000-0002-5157-0076
Lance C KamDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID 0000-0001-6812-4956
Morgan HuseImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. husem@mskcc.org.ORCID 0000-0001-9941-7719
Memorial Sloan Kettering Cancer Center · USColumbia University · USBrookhaven National Laboratory · USCornell University · USHoward Hughes Medical Institute · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Synaptic Control of Cytotoxic T cell FunctionR01AI087644 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI HUSE, MORGAN A · 2010 to 2025
$7.3M
Advanced Rigidity-based Material for Enhanced ImmunotherapyR01AI110593 · NIAID · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI KAM, LANCE C · 2015 to 2018
$1.6M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA008748NIAID NIH HHS R01 AI087644NIAID NIH HHS R01 AI110593
6 · The paper itself

Abstract

Cytotoxic T lymphocytes (CTLs) kill by forming immunological synapses with target cells and secreting toxic proteases and the pore-forming protein perforin into the intercellular space. Immunological synapses are highly dynamic structures that boost perforin activity by applying mechanical force against the target cell. Here, we used high-resolution imaging and microfabrication to investigate how CTLs exert synaptic forces and coordinate their mechanical output with perforin secretion. Using micropatterned stimulatory substrates that enable synapse growth in three dimensions, we found that perforin release occurs at the base of actin-rich protrusions that extend from central and intermediate locations within the synapse. These protrusions, which depended on the cytoskeletal regulator WASP and the Arp2/3 actin nucleation complex, were required for synaptic force exertion and efficient killing. They also mediated physical deformation of the target cell surface during CTL-target cell interactions. Our results reveal the mechanical basis of cellular cytotoxicity and highlight the functional importance of dynamic, three-dimensional architecture in immune cell-cell interfaces.

Indexed as

Actin-Related Protein 2-3 ComplexActinsAnimalsImmunological SynapsesMicePerforinT-Lymphocytes, CytotoxicWiskott-Aldrich Syndrome ProteinActin-Related Protein 2-3 ComplexActinsPerforinWiskott-Aldrich Syndrome Protein

Identifiers

PMID30902904
PMCPMC6746172
OpenAlexW2897545405

What OpenQuestion holds

Textmetadata
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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.