Evidence map›Paper›PMID 30564890›Full record

ArticleCancer immunology, immunotherapy : CII2019

Identification and characterization of an alternative cancer-derived PD-L1 splice variant.

Nadia B Hassounah, Venkat S Malladi, Yi Huang, Samuel S Freeman, Ellen M Beauchamp, Shohei Koyama, Nicholas Souders, Sunil Martin, Glenn Dranoff, Kwok-Kin Wong and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 5 pooled it
–field-weighted citation impact
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

56 citing papers in PubMed, 5 syntheses or guidelines pooled it.

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  13. Therapeutic implications for the PD-1 axis in cerebrovascular injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
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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.

Nadia B HassounahDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Venkat S MalladiDepartment of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yi HuangDepartment of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.
Samuel S FreemanCancer Program, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Ellen M BeauchampDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Shohei KoyamaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nicholas SoudersDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sunil MartinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Glenn DranoffDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kwok-Kin WongDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Chandra S PedamalluDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Peter S HammermanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Esra A AkbayDepartment of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA. esra.akbay@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-4149-2529

Funding

UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V., MINNA, JOHN D. · 1996 to 2024
$57.4M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Therapeutic approaches for LKB1-deficient non-small cell lung cancerR01CA205150 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HEYMACH, JOHN V., WONG, KWOK KIN · 2016 to 2020
$3.0M
Therapeutic targeting of Fibroblast Growth Factor Receptors in Squamous CancersR01CA196932 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2015 to 2019
$1.9M
Genomic Discovery and Targeted Therapeutics in Squamous Cell Lung CancerK08CA163677 · NCI · DANA-FARBER CANCER INST · PI HAMMERMAN, PETER S · 2012 to 2016
$783k
Ultrasensitive identification and precise quantitation of low frequency somatic mR21CA160080 · NCI · UNIVERSITY OF WASHINGTON · PI SHENDURE, JAY ASHOK · 2011 to 2013
$588k
NCI NIH HHS 5P50CA070907NCI NIH HHS CA196932NCI NIH HHS CA205150NCI NIH HHS K08 CA163677NCI NIH HHS P50 CA070907NCI NIH HHS R01 CA196932NCI NIH HHS R01 CA205150NHGRI NIH HHS T32 HG002295
6 · The paper itself

Abstract

Therapeutic blockade of the PD-1/PD-L1 axis is recognized as an effective treatment for numerous cancer types. However, only a subset of patients respond to this treatment, warranting a greater understanding of the biological mechanisms driving immune evasion via PD-1/PD-L1 signaling and other T-cell suppressive pathways. We previously identified a head and neck squamous cell carcinoma with human papillomavirus integration in the PD-L1 locus upstream of the transmembrane domain-encoding region, suggesting expression of a truncated form of PD-L1 (Parfenov et al., Proc Natl Acad Sci USA 111(43):15544-15549, 2014). In this study, we extended this observation by performing a computational analysis of 33 other cancer types as well as human cancer cell lines, and identified additional PD-L1 isoforms with an exon 4 enrichment expressed in 20 cancers and human cancer cell lines. We demonstrate that cancer cell lines with high expression levels of exon 4-enriched PD-L1 generate a secreted form of PD-L1. Further biochemical studies of exon 4-enriched PD-L1 demonstrated that this form is secreted and maintains the capacity to bind PD-1 as well as to serve as a negative regulator on T cell function, as measured by inhibition of IL-2 and IFNg secretion. Overall, we have demonstrated that truncated forms of PD-L1 exist in numerous cancer types, and have validated that truncated PD-L1 can be secreted and negatively regulate T cell function.

Indexed as

Alternative SplicingB7-H1 AntigenCell Line, TumorExonsHumansInterferon-gammaLymphokinesProtein IsoformsB7-H1 AntigenInterferon-gammainterleukin 2 inhibitorLymphokinesProtein IsoformsCancer immunologyHPVPD-L1Secreted PD-L1

Identifiers

PMID30564890
PMCPMC6428600

What OpenQuestion holds

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Registered trials

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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.