Evidence map›Paper›PMID 33324999›Full record

ArticleVirchows Archiv : an international journal of pathology2021

Comparative analysis of post-transplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation reveals differences in the tumor microenvironment.

Mathis Overkamp, Massimo Granai, Irina Bonzheim, Julia Steinhilber, Jens Schittenhelm, Wolfgang Bethge, Leticia Quintanilla-Martinez, Falko Fend, Birgit Federmann

Open access · hybridAbstract readComparative Study
In one paragraph

Article in Virchows Archiv : an international journal of pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 38% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
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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.

Mathis OverkampInstitute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany.
Massimo GranaiInstitute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany.
Irina BonzheimInstitute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany.
Julia SteinhilberInstitute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany.
Jens SchittenhelmInstitute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany.
Wolfgang BethgeDepartment of Internal Medicine Hematology and Oncology, Comprehensive Cancer Center and University Hospital Tuebingen, Tuebingen, Germany.
Leticia Quintanilla-MartinezInstitute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany.
Falko FendInstitute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany.
Birgit FedermannInstitute of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany. birgit.federmann@med.uni-tuebingen.de.
University of Siena · IT

Funding

University of Tuebingen University of Tuebingen, TÜFF-program, project 2320-0-0
6 · The paper itself

Abstract

Post-transplant lymphoproliferative disorders (PTLD) occur after solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HCT) and are frequently associated with Epstein-Barr virus (EBV). Because of the complex immune setup in PTLD patients, the tumor microenvironment (TME) is of particular interest to understand PTLD pathogenesis and elucidate predictive factors and possible treatment options. We present a comparative study of clinicopathological features of 48 PTLD after HCT (n = 26) or SOT (n = 22), including non-destructive (n = 6), polymorphic (n = 23), and monomorphic (n = 18) PTLD and classic Hodgkin lymphoma (n = 1). EBV was positive in 35 cases (73%). A detailed examination of the TME with image analysis-based quantification in 22 cases revealed an inflammatory TME despite underlying immunosuppression and significant differences in its density and composition depending on type of transplant, PTLD subtypes, and EBV status. Tumor-associated macrophages (TAMs) expressing CD163 (p = 0.0022) and Mannose (p = 0.0016) were enriched in PTLD after HCT. Double stains also showed differences in macrophage polarization, with more frequent M1 polarization after HCT (p = 0.0321). Higher counts for TAMs (CD163 (p = 0.0008) and cMaf (p = 0.0035)) as well as in the T cell compartment (Granzyme B (p = 0.0028), CD8 (p = 0.01), and for PD-L1 (p = 0.0305)) were observed depending on EBV status. In conclusion, despite the presence of immunosuppression, PTLD predominantly contains an inflammatory TME characterized by mostly M1-polarized macrophages and cytotoxic T cells. Status post HCT, EBV positivity, and polymorphic subtype are associated with an actively inflamed TME, indicating a specific response of the immune system. Further studies need to elucidate prognostic significance and potential therapeutic implications of the TME in PTLD.

Indexed as

AdolescentAdultAgedChildChild, PreschoolEpstein-Barr Virus InfectionsFemaleHematopoietic Stem Cell TransplantationHerpesvirus 4, HumanHumansInfantLymphoproliferative DisordersMaleMiddle AgedOrgan TransplantationTransplantation, HomologousHematopoietic stem cell transplantationMacrophagesMicroenvironmentPost-transplant lymphoproliferative diseaseSolid organ transplantation

Identifiers

PMID33324999
PMCPMC8203555
OpenAlexW3111024142

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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.