Evidence map›Paper›PMID 36726072›Full record

ArticleBMC cancer2023

Characterisation of tumour-immune phenotypes and PD-L1 positivity in squamous bladder cancer.

Max Jung, Michael Rose, Ruth Knuechel, Chiara Loeffler, Hannah Muti, Jakob Nikolas Kather, Nadine T Gaisa, German Study Group of Bladder Cancer (DFBK e.V.)

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. PD-L1International journal of molecular sciences · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Article
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

8 authors at 2 institutions in 1 country.

Max JungInstitute of Pathology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
Michael RoseInstitute of Pathology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
Ruth KnuechelInstitute of Pathology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
Chiara LoefflerDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Hannah MutiDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Jakob Nikolas KatherDepartment of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
Nadine T GaisaInstitute of Pathology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. ngaisa@ukaachen.de.
German Study Group of Bladder Cancer (DFBK e.V.)
RWTH Aachen University · DEUniversity Hospital Carl Gustav Carus · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsImmune checkpoint inhibitor (ICI) therapy has become a viable treatment strategy in bladder cancer. However, treatment responses vary, and improved biomarkers are needed. Crucially, the characteristics of immune cells remain understudied especially in squamous differentiated bladder cancer (sq-BLCA). Here, we quantitatively analysed the tumour-immune phenotypes of sq-BLCA and correlated them with PD-L1 expression and FGFR3 mutation status.

methodsTissue microarrays (TMA) of n = 68 non-schistosomiasis associated pure squamous cell carcinoma (SCC) and n = 46 mixed urothelial carcinoma with squamous differentiation (MIX) were subjected to immunohistochemistry for CD3, CD4, CD8, CD56, CD68, CD79A, CD163, Ki67, perforin and chloroacetate esterase staining. Quantitative image evaluation was performed via digital image analysis.

resultsImmune infiltration was generally higher in stroma than in tumour regions. B-cells (CD79A) were almost exclusively found in stromal areas (sTILs), T-lymphocytes and macrophages were also present in tumour cell areas (iTILs), while natural killer cells (CD56) were nearly missing in any area. Tumour-immune phenotype distribution differed depending on the immune cell subset, however, hot tumour-immune phenotypes (high density of immune cells in tumour areas) were frequently found for CD8 + T-cells (33%), especially perforin + lymphocytes (52.2%), and CD68 + macrophages (37.6%). Perforin + CD8 lymphocytes predicted improved overall survival in sq-BLCA while high PD-L1 expression (CPS ≥ 10) was significantly associated with higher CD3 + , CD8 + and CD163 + immune cell density and high Ki67 (density) of tumour cells. Furthermore, PD-L1 expression was positively associated with CD3 + /CD4 + , CD3 + /CD8 + and CD68 + /CD163 + hot tumour-immune phenotypes. FGFR3 mutation status was inversely associated with CD8 + , perforin + and CD79A + lymphocyte density.

conclusionsComputer-based image analysis is an efficient tool to analyse immune topographies in squamous bladder cancer. Hot tumour-immune phenotypes with strong PD-L1 expression might pose a promising subgroup for clinically successful ICI therapy in squamous bladder cancer and warrant further investigation.

Indexed as

Carcinoma, Squamous CellCarcinoma, Transitional CellUrinary Bladder NeoplasmsB7-H1 AntigenBiomarkers, TumorCD8-Positive T-LymphocytesHumansKi-67 AntigenLymphocytes, Tumor-InfiltratingPerforinPhenotypeTumor MicroenvironmentB7-H1 AntigenBiomarkers, TumorKi-67 AntigenPerforinBladder cancerImmune cell infiltratePD-L1Squamous cell carcinoma of the bladder

Identifiers

PMID36726072
PMCPMC9890720
OpenAlexW4318777238

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LicenceCC BY
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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.