Evidence map›Paper›PMID 36793050›Full record

ArticleJournal of translational medicine2023

Tumor-associated macrophages and Tregs influence and represent immune cell infiltration of muscle-invasive bladder cancer and predict prognosis.

Florestan J Koll, Severine Banek, Luis Kluth, Jens Köllermann, Katrin Bankov, Felix K-H Chun, Peter J Wild, Andreas Weigert, Henning Reis

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
15.2field-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.

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

28 citing papers in PubMed, 48 citations in OpenAlex.

  1. Trial
  2. The M1/M2 Test System for Determining Macrophage Phenotypes.International journal of molecular sciences · 2026
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  7. [Pirfenidone inhibits bladder cancer xenograft growth in mice by regulating regulatory T cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 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

9 authors at 1 institution in 1 country.

Florestan J KollDepartment of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. florestanjohannes.koll@kgu.de.ORCID 0000-0001-7828-3950
Severine BanekDepartment of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
Luis KluthDepartment of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
Jens KöllermannDr. Senckenberg Institute of Pathology, University Hospital Frankfurt, 60590, Frankfurt am Main, Germany.
Katrin BankovDr. Senckenberg Institute of Pathology, University Hospital Frankfurt, 60590, Frankfurt am Main, Germany.
Felix K-H ChunDepartment of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
Peter J WildFrankfurt Cancer Institute (FCI), University Hospital, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
Andreas WeigertInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
Henning ReisDr. Senckenberg Institute of Pathology, University Hospital Frankfurt, 60590, Frankfurt am Main, Germany.
Goethe University Frankfurt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

INTRODUCTION AND

objectiveMuscle-invasive urothelial bladder cancer (MIBC) is associated with limited response rates to systemic therapy, risk of recurrence and death. Tumor infiltrating immune cells have been associated with outcome and response to chemo-and immunotherapy in MIBC. We aimed to profile the immune cells in the tumor microenvironment (TME) to predict prognosis in MIBC and responses to adjuvant chemotherapy.

methodsWe performed multiplex immunohistochemistry (IHC) profiling and quantification of immune and stromal cells (CD3, CD4, CD8, CD163, FoxP3, PD-1, and CD45, Vimentin, αSMA, PD-L1, Pan-Cytokeratin, Ki67) in 101 patients with MIBC receiving radical cystectomy. We used uni- and multivariate survival analyses to identify cell types predicting prognosis. Samples were subdivided using K-means clustering for Treg and macrophage infiltration resulting in 3 clusters, Cluster 1: Treg high, cluster 2: macrophage high, cluster 3: Treg and macrophage low. Routine CD68 and CD163 IHC were analyzed with QuPath in an extended cohort of 141 MIBC.

resultsHigh concentrations of macrophages were associated with increased risk of death (HR 10.9, 95% CI 2.8-40.5; p < 0.001) and high concentrations of Tregs were associated with decreased risk of death (HR 0.1, 95% CI 0.01-0.7; p = 0.03) in the multivariate Cox-regression model adjusting for adjuvant chemotherapy, tumor and lymph node stage. Patients in the macrophage rich cluster (2) showed the worst OS with and without adjuvant chemotherapy. The Treg rich cluster (1) showed high levels of effector and proliferating immune cells and had the best survival. Cluster 1 and 2 both were rich in PD-1 and PD-L1 expression on tumor and immune cells.

conclusionTreg and macrophage concentrations in MIBC are independent predictors of prognosis and are important players in the TME. Standard IHC with CD163 for macrophages is feasible to predict prognosis but validation to use immune-cell infiltration, especially to predict response to systemic therapies, is required.

Indexed as

B7-H1 AntigenT-Lymphocytes, RegulatoryTumor-Associated MacrophagesUrinary Bladder NeoplasmsHumansMusclesPrognosisProgrammed Cell Death 1 ReceptorTumor MicroenvironmentB7-H1 AntigenProgrammed Cell Death 1 ReceptorBladder cancerChemotherapyImmune cellsMIBCTAMTreg

Identifiers

PMID36793050
PMCPMC9930232
OpenAlexW4321002378

What OpenQuestion holds

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LicenceCC BY
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.