Evidence map›Paper›PMID 26260996›Full record

ArticleProstate cancer and prostatic diseases2015

Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance.

A M Martin, T R Nirschl, C J Nirschl, B J Francica, C M Kochel, A van Bokhoven, A K Meeker, M S Lucia, R A Anders, A M DeMarzo and 1 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Prostate cancer and prostatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03835533 (A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer), which is not on this map. Cited by 115 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 6 pooled it
6.0field-weighted citation impact, top 2% 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.

NCT03835533 phase1completednot on this mapstarted 2019, after this paper: background citation

A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer

TypeinterventionalSponsorParker Institute for Cancer ImmunotherapyRan2019 to 2022Enrolled43ConditionsMetastatic Castration-resistant Prostate CancerArmsNKTR-214 (Cohort A), Nivolumab (Cohort A, B and C), Stereotactic body radiation therapy (SBRT) (Cohort B), CDX-301 (Cohort B and C), Poly-ICLC (Cohort B)
3 · Its place in the literature

Who cites it

115 citing papers in PubMed, 6 syntheses or guidelines pooled it, 184 citations in OpenAlex.

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  18. CBP/p300, a promising therapeutic target for prostate cancer.Journal of translational medicine · 2025
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55 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

11 authors at 1 institution in 1 country.

A M MartinDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
T R NirschlDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
C J NirschlDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
B J FrancicaDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
C M KochelDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
A van BokhovenDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
A K MeekerDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
M S LuciaDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
R A AndersDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
A M DeMarzoDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
C G DrakeDepartment of Oncology, Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
TRANSGENIC MODELS FOR PROSTATE CANCER AND AUTOIMMUNITYP50CA058236 · NCI · JOHNS HOPKINS UNIVERSITY · PI ISAACS, JOHN TOD · 1992 to 2020
$43.9M
LAB RESEARCH TRAINING IN PEDIATRIC ONCOLOGY-HEMATOLOGYT32CA060441 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN D FRIEDMAN · 1993 to 2026
$14.9M
CELLULAR &MOLECULAR MECH OF INFLAMMATORY REACTIONST32AI007247 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Joel L Pomerantz · 1985 to 2026
$10.2M
Analysis of Lag-3 in Regulatory T Cell Function and Immune SupressionR01CA127153 · NCI · JOHNS HOPKINS UNIVERSITY · PI DRAKE, CHARLES G. · 2008 to 2012
$1.7M
NCI NIH HHS 1P50CA58236-15NCI NIH HHS NIH P30 CA006973NCI NIH HHS NIH P30CA046934NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA046934NCI NIH HHS P50 CA058236NCI NIH HHS R01 CA127153NCI NIH HHS R01CA127153NIAID NIH HHS T32 AI007247
6 · The paper itself

Abstract

backgroundPrimary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation--constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss.

methodsHuman prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples.

resultsIn vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss.

conclusionsThese studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.

Indexed as

Adaptive ImmunityImmunity, InnateAnilidesAntineoplastic AgentsB7-H1 AntigenBiomarkersCell Line, TumorFlow CytometryGene Expression Regulation, NeoplasticHumansImmunohistochemistryInterferon-gammaMaleNitrilesProstatic NeoplasmsPTEN PhosphohydrolaseAnilidesAntineoplastic AgentsB7-H1 AntigenbicalutamideBiomarkersInterferon-gammaNitrilesPTEN PhosphohydrolasePTEN protein, humanTosyl Compounds

Identifiers

PMID26260996
PMCPMC4641011
OpenAlexW2344610509

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Registered trials

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.