Evidence map›Paper›PMID 28280247›Full record

ArticleScience (New York, N.Y.)2017

T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition.

Enfu Hui, Jeanne Cheung, Jing Zhu, Xiaolei Su, Marcus J Taylor, Heidi A Wallweber, Dibyendu K Sasmal, Jun Huang, Jeong M Kim, Ira Mellman and 1 more

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

Article in Science (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 993 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
993citing papers in PubMed, 5 pooled it
70.1field-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

993 citing papers in PubMed, 5 syntheses or guidelines pooled it, 1,623 citations in OpenAlex.

  1. Pooled it
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  4. Pooled it
  5. Pooled it
  6. Trial
  7. Biochemistry and biophysics reports · 2026
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  16. Decoding T cell exhaustion in the tumour microenvironment.Experimental & molecular medicine · 2026
    Review
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933 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Enfu HuiDepartment of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.ORCID 0000-0001-7876-2783
Jeanne CheungDepartment of Cancer Immunology, Genentech, South San Francisco, CA 94080, USA.ORCID 0000-0001-7969-2449
Jing ZhuDepartment of Cancer Immunology, Genentech, South San Francisco, CA 94080, USA.
Xiaolei SuDepartment of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.ORCID 0000-0001-8696-7922
Marcus J TaylorDepartment of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA.
Heidi A WallweberDepartment of Cancer Immunology, Genentech, South San Francisco, CA 94080, USA.ORCID 0000-0002-9844-6611
Dibyendu K SasmalInstitute for Molecular Engineering, University of Chicago, IL 60637, USA.
Jun HuangInstitute for Molecular Engineering, University of Chicago, IL 60637, USA.
Jeong M KimDepartment of Cancer Immunology, Genentech, South San Francisco, CA 94080, USA.
Ira MellmanDepartment of Cancer Immunology, Genentech, South San Francisco, CA 94080, USA. mellman.ira@gene.com ron.vale@ucsf.edu.ORCID 0000-0002-6132-7299
Ronald D ValeDepartment of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. mellman.ira@gene.com ron.vale@ucsf.edu.ORCID 0000-0003-3460-2758
Howard Hughes Medical Institute · USUniversity of Chicago · US

Funding

MICROTUBULE-BASED ORGANELLE TRANSPORTR01GM038499 · NIGMS · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI VALE, RONALD D · 1988 to 2005
$1.2M
Recognition of cross-reactive antigens by human CD4+ T cellsR00AI106941 · NIAID · UNIVERSITY OF CHICAGO · PI HUANG, JUN · 2015 to 2016
$497k
Direct visualization of serial engagement by T cell receptorsR21AI120010 · NIAID · UNIVERSITY OF CHICAGO · PI HUANG, JUN · 2015 to 2016
$425k
NIAID NIH HHS R00 AI106941NIAID NIH HHS R21 AI120010NIGMS NIH HHS R01 GM038499
6 · The paper itself

Abstract

Programmed cell death-1 (PD-1) is a coinhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). By titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1-recruited Shp2 phosphatase. We also show that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system. These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that costimulatory pathways play key roles in regulating effector T cell function and responses to anti-PD-L1/PD-1 therapy.

Indexed as

AnimalsB7-H1 AntigenCD28 AntigensHumansImmunotherapyJurkat CellsLymphocyte ActivationMiceMice, Inbred C57BLNeoplasmsPhosphorylationProgrammed Cell Death 1 ReceptorT-LymphocytesB7-H1 AntigenCD274 protein, humanCD28 AntigensProgrammed Cell Death 1 Receptor

Identifiers

PMID28280247
PMCPMC6286077
OpenAlexW2592133876

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.