Evidence map›Paper›PMID 29416939›Full record

ArticleOncoimmunology

Maturation of tertiary lymphoid structures and recurrence of stage II and III colorectal cancer.

Florian Posch, Karina Silina, Sebastian Leibl, Axel Mündlein, Holger Moch, Alexander Siebenhüner, Panagiotis Samaras, Jakob Riedl, Michael Stotz, Joanna Szkandera and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 270 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
270citing papers in PubMed, 6 pooled it
6.9field-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.

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

270 citing papers in PubMed, 6 syntheses or guidelines pooled it, 356 citations in OpenAlex.

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210 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

18 authors at 4 institutions in 3 countries.

Florian PoschDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
Karina SilinaTumor Immunology Research Unit, Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland.
Sebastian LeiblDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, Zürich, Switzerland.
Axel MündleinVorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, Feldkirch, Austria.
Holger MochDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, Zürich, Switzerland.
Alexander SiebenhünerDepartment of Oncology, University Hospital Zurich, Rämistrasse 100, Zürich, Switzerland.
Panagiotis SamarasDepartment of Oncology, University Hospital Zurich, Rämistrasse 100, Zürich, Switzerland.
Jakob RiedlDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
Michael StotzDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
Joanna SzkanderaDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
Herbert StögerDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
Martin PichlerDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
Roger StuppDepartment of Oncology, University Hospital Zurich, Rämistrasse 100, Zürich, Switzerland.
Maries van den BroekTumor Immunology Research Unit, Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland.
Peter SchramlDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstrasse 12, Zürich, Switzerland.
Armin GergerDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria.
Ulf PetrauschDepartment of Oncology, University Hospital Zurich, Rämistrasse 100, Zürich, Switzerland.
Thomas WinderVorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, Feldkirch, Austria.
Medical University of Graz · ATUniversity Hospital of Zurich · CHUniversity of Zurich · CHVorarlberg Institute for Vascular Investigation and Treatment · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers. TLS formed in most tumors and were significantly more prevalent in highly-microsatellite-instable (MSI-H) and/or BRAF-mutant nmCRC. We could distinguish three sequential TLS maturation stages which were characterized by increasing prevalence of FDCs and mature B-cells: [1] Early TLS, composed of dense lymphocytic aggregates without FDCs, [2] Primary follicle-like TLS, having FDCs but no GC reaction, and [3] Secondary follicle-like TLS, having an active GC reaction. A simple integrated TLS immunoscore reflecting these parameters identified a large subgroup of nmCRC patients with a very low risk of recurrence independently of clinical co-variables such as ECOG performance status, age, stage, and adjuvant chemotherapy. We conclude that (1) mismatch repair and BRAF mutation status are associated with the formation of TLS in nmCRC, (2) TLS formation in nmCRC follows sequential maturation steps, culminating in germinal center formation, and (3) this maturation process harbors important prognostic information on the risk of disease recurrence.

Indexed as

colorectal cancerCrohn's-like reactiongerminal centerimmunoscorerecurrencerisk factorstructural equation modeltertiary lymphoid structures

Identifiers

PMID29416939
PMCPMC5798199
OpenAlexW2754092421

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.