Evidence map›Paper›PMID 26801886›Full record

ArticleGut2017

Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma.

Elizabeth D Thompson, Marianna Zahurak, Adrian Murphy, Toby Cornish, Nathan Cuka, Eihab Abdelfatah, Stephen Yang, Mark Duncan, Nita Ahuja, Janis M Taube and 2 more

3 registry-linked trialsAbstract read
In one paragraph

Article in Gut, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 296 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
296citing papers in PubMed, 5 pooled it
23.3field-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.

NCT03044613 phase1active not recruitingnot on this map

Phase IB Trial of Induction Nivolumab or Nivolumab/Relatlimab Prior to Concurrent Chemoradiation in Patients With Operable Stage II/III Esophageal/ Gastroesophageal Junction Cancer

TypeinterventionalSponsorSidney Kimmel Comprehensive Cancer Center at Johns HopkinsRan2017 to 2027Enrolled32ConditionsGastric Cancer, Esophageal Cancer, GastroEsophageal CancerArmsNivolumab, Relatlimab, Carboplatin, Paclitaxel, Radiation
NCT03610711 phase1 / phase2active not recruitingnot on this mapstarted 2019, after this paper: background citation

REACTION (Radiation Enhanced Assessment of Combination Therapies in Immuno-ONcology) - Nivolumab or Nivolumab in Combination With Other Immuno-oncology (IO) Agents After Targeted Systemic Radiation in Patients With Advanced Esophagogastric Cancer

TypeinterventionalSponsorSidney Kimmel Comprehensive Cancer Center at Johns HopkinsRan2019 to 2027Enrolled21ConditionsGastroesophageal Cancer, Immune Checkpoint InhibitionArmsNivolumab, Relatlimab
NCT03651271 phase2completednot on this mapstarted 2018, after this paper: background citation

An Exploratory Study of Nivolumab With or Without Ipilimumab According to the Percentage of Tumoral CD8 Cells in Participants With Advanced Metastatic Cancer

TypeinterventionalSponsorParker Institute for Cancer ImmunotherapyRan2018 to 2023Enrolled100ConditionsAdvanced Metastatic Cancer, Advanced Prostate CancerArmsNivolumab Monotherapy, Nivolumab and Ipilimumab and Combination for Metastatic Cancer, Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer, Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer
3 · Its place in the literature

Who cites it

296 citing papers in PubMed, 5 syntheses or guidelines pooled it, 490 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Review
  11. Article
  12. Review
  13. CD8Cancer science · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Elizabeth D ThompsonDepartment of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Marianna ZahurakDivision of Biostatistics and Bioinformatics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Adrian MurphyDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Toby CornishDepartment of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Nathan CukaDepartment of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Eihab AbdelfatahDepartment of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Stephen YangDepartment of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Mark DuncanDepartment of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Nita AhujaDepartment of Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Janis M TaubeDepartment of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Robert A AndersDepartment of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Ronan J KellyDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Johns Hopkins Hospital · USJohns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI LENNON, ANNE MARIE · 1993 to 2022
$54.6M
Clinical and Laboratory Research Training for Surgical OncologistsT32CA126607 · NCI · JOHNS HOPKINS UNIVERSITY · PI CAMERON, ANDREW M. · 2008 to 2024
$6.0M
NCI NIH HHS P30 CA006973NCI NIH HHS P50 CA062924NCI NIH HHS T32 CA126607
6 · The paper itself

Abstract

objectiveRecent data supports a significant role for immune checkpoint inhibitors in the treatment of solid tumours. Here, we evaluate gastric and gastro-oesophageal junction (G/GEJ) adenocarcinomas for their expression of programmed death-ligand 1 (PD-L1), infiltration by CD8+ T cells and the relationship of both factors to patient survival.

designThirty-four resections of primary invasive G/GEJ were stained by immunohistochemistry for PD-L1 and CD8 and by DNA in situ hybridisation for Epstein-Barr virus (EBV). CD8+ T cell densities both within tumours and at the tumour-stromal interface were analysed using whole slide digital imaging. Patient survival was evaluated according to PD-L1 status and CD8 density.

results12% of resections showed tumour cell membranous PD-L1 expression and 44% showed expression within the immune stroma. Two cases (6%) were EBV positive, with one showing membranous PD-L1 positivity. Increasing CD8+ densities both within tumours and immune stroma was associated with increasing percentage of tumour (p=0.027) and stromal (p=0.005) PD-L1 expression. Both tumour and immune stromal PD-L1 expression and high intratumoral or stromal CD8+ T cell density (>500/mm

conclusionsPD-L1 is expressed on both tumour cells and in the immune stroma across all stages and histologies of G/GEJ. Surprisingly, we demonstrate that increasing CD8 infiltration is correlated with impaired PFS and OS. Patients with higher CD8+ T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. Further characterisation of the G/GEJ immune microenvironment may highlight targets for immune-based therapy.

Indexed as

Herpesvirus 4, HumanAdenocarcinomaAdultAgedAged, 80 and overB7-H1 AntigenCD8-Positive T-LymphocytesDisease-Free SurvivalDNA, ViralEsophagogastric JunctionFemaleHumansLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm InvasivenessB7-H1 AntigenCD274 protein, humanDNA, ViralCANCER IMMUNOBIOLOGYGASTRIC CANCERIMMUNE RESPONSEIMMUNOTHERAPY

Identifiers

PMID26801886
PMCPMC4958028
OpenAlexW2298468092

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.