Evidence map›Paper›PMID 32437509›Full record

ArticleThe Journal of cell biology2020

PD-1 and BTLA regulate T cell signaling differentially and only partially through SHP1 and SHP2.

Xiaozheng Xu, Bowen Hou, Amitkumar Fulzele, Takeya Masubuchi, Yunlong Zhao, Zijun Wu, Yanyan Hu, Yong Jiang, Yanzhe Ma, Haopeng Wang and 3 more

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

Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 3% 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

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.

  1. Pooled it
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  14. MutantFrontiers in immunology · 2026
    Article
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20 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

13 authors at 3 institutions in 2 countries.

Xiaozheng XuDivision of Biological Sciences, University of California San Diego, La Jolla, CA.
Bowen HouSchool of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Amitkumar FulzeleDivision of Biological Sciences, University of California San Diego, La Jolla, CA.
Takeya MasubuchiDivision of Biological Sciences, University of California San Diego, La Jolla, CA.
Yunlong ZhaoDivision of Biological Sciences, University of California San Diego, La Jolla, CA.
Zijun WuDivision of Biological Sciences, University of California San Diego, La Jolla, CA.
Yanyan HuSchool of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Yong JiangSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Yanzhe MaDivision of Biological Sciences, University of California San Diego, La Jolla, CA.
Haopeng WangSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Eric J BennettDivision of Biological Sciences, University of California San Diego, La Jolla, CA.
Guo FuSchool of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Enfu HuiDivision of Biological Sciences, University of California San Diego, La Jolla, CA.
University of California San Diego · USXiamen University · CNShanghaiTech University · CN

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
Regulation of PD-L1/PD-1 immune checkpoints by cis-interactionsR37CA239072 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HUI, ENFU · 2019 to 2025
$2.5M
NCI NIH HHS P30 CA023100NCI NIH HHS R37 CA239072
6 · The paper itself

Abstract

Blockade antibodies of the immunoinhibitory receptor PD-1 can stimulate the anti-tumor activity of T cells, but clinical benefit is limited to a fraction of patients. Evidence suggests that BTLA, a receptor structurally related to PD-1, may contribute to resistance to PD-1 targeted therapy, but how BTLA and PD-1 differ in their mechanisms is debated. Here, we compared the abilities of BTLA and PD-1 to recruit effector molecules and to regulate T cell signaling. While PD-1 selectively recruited SHP2 over the stronger phosphatase SHP1, BTLA preferentially recruited SHP1 to more efficiently suppress T cell signaling. Contrary to the dominant view that PD-1 and BTLA signal exclusively through SHP1/2, we found that in SHP1/2 double-deficient primary T cells, PD-1 and BTLA still potently inhibited cell proliferation and cytokine production, albeit more transiently than in wild type T cells. Thus, PD-1 and BTLA can suppress T cell signaling through a mechanism independent of both SHP1 and SHP2.

Indexed as

AnimalsCD3 ComplexCell ProliferationChromatography, LiquidCytokinesFluorescence Resonance Energy TransferGene Knockout TechniquesHEK293 CellsHumansInterleukin-2Jurkat CellsMiceMice, Inbred C57BLMice, KnockoutMutationProgrammed Cell Death 1 ReceptorBTLA protein, humanCD3 ComplexCytokinesInterleukin-2Programmed Cell Death 1 ReceptorProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6PTPN11 protein, humanReceptors, ImmunologicRecombinant Proteins

Identifiers

PMID32437509
PMCPMC7265324
OpenAlexW3028144130

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.