Evidence map›Paper›PMID 38720314›Full record

ArticleMolecular cancer2024

Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells.

Lisa-Marie Rieckmann, Michael Spohn, Lisa Ruff, David Agorku, Lisa Becker, Alina Borchers, Jenny Krause, Roisin O'Reilly, Jurek Hille, Janna-Lisa Velthaus-Rusik and 22 more

Abstract readLetter
In one paragraph

Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026
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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

32 authors.

Lisa-Marie Rieckmann *Department of Personalized Oncology, DKFZ-Hector Cancer Institute, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Michael Spohn *Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Lisa Ruff *Department of Personalized Oncology, DKFZ-Hector Cancer Institute, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
David AgorkuMiltenyi Biotec B.V. & Co. KG, R&D, Bergisch Gladbach, Germany.
Lisa BeckerHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH), Heidelberg, Germany.
Alina BorchersIII. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jenny KrauseI. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Roisin O'ReillyDepartment of Personalized Oncology, DKFZ-Hector Cancer Institute, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Jurek HilleDepartment of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Janna-Lisa Velthaus-RusikDepartment of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Niklas BeumerDepartment of Personalized Oncology, DKFZ-Hector Cancer Institute, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Armin GüntherDepartment of Personalized Oncology, DKFZ-Hector Cancer Institute, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Lena WillnowDepartment of Personalized Oncology, DKFZ-Hector Cancer Institute, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Charles D ImbuschDivision of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Peter IglauerInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Ronald SimonInstitute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sören FranzenburgInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany.
Hauke WinterTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Department of Thoracic Oncology, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
Michael ThomasTranslational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Department of Thoracic Oncology, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
Carsten BokemeyerDepartment of Oncology, Hematology and Bone Marrow Transplantation With Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nicola GaglianiHamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Christian F KrebsIII. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Martin SprickHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH), Heidelberg, Germany.
Olaf HardtMiltenyi Biotec B.V. & Co. KG, R&D, Bergisch Gladbach, Germany.
Sabine RiethdorfDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Andreas TrumppHeidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH), Heidelberg, Germany.
Nikolas H StoeckleinGeneral, Visceral and Pediatric Surgery, University Hospital and Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Sven PeineInstitute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Philipp RosenstielInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany.
Klaus PantelDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sonja Loges *Department of Personalized Oncology, DKFZ-Hector Cancer Institute, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Melanie Janning *Department of Personalized Oncology, DKFZ-Hector Cancer Institute, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. melanie.janning@dkfz-heidelberg.de.

Funding

European Research Council 758713-ELIMINATE
6 · The paper itself

Abstract

backgroundCirculating tumor cells (CTCs) hold immense promise for unraveling tumor heterogeneity and understanding treatment resistance. However, conventional methods, especially in cancers like non-small cell lung cancer (NSCLC), often yield low CTC numbers, hindering comprehensive analyses. This study addresses this limitation by employing diagnostic leukapheresis (DLA) to cancer patients, enabling the screening of larger blood volumes. To leverage DLA's full potential, this study introduces a novel approach for CTC enrichment from DLAs.

methodsDLA was applied to six advanced stage NSCLC patients. For an unbiased CTC enrichment, a two-step approach based on negative depletion of hematopoietic cells was used. Single-cell (sc) whole-transcriptome sequencing was performed, and CTCs were identified based on gene signatures and inferred copy number variations.

resultsRemarkably, this innovative approach led to the identification of unprecedented 3,363 CTC transcriptomes. The extensive heterogeneity among CTCs was unveiled, highlighting distinct phenotypes related to the epithelial-mesenchymal transition (EMT) axis, stemness, immune responsiveness, and metabolism. Comparison with sc transcriptomes from primary NSCLC cells revealed that CTCs encapsulate the heterogeneity of their primary counterparts while maintaining unique CTC-specific phenotypes.

conclusionsIn conclusion, this study pioneers a transformative method for enriching CTCs from DLA, resulting in a substantial increase in CTC numbers. This allowed the creation of the first-ever single-cell whole transcriptome in-depth characterization of the heterogeneity of over 3,300 NSCLC-CTCs. The findings not only confirm the diagnostic value of CTCs in monitoring tumor heterogeneity but also propose a CTC-specific signature that can be exploited for targeted CTC-directed therapies in the future. This comprehensive approach signifies a major leap forward, positioning CTCs as a key player in advancing our understanding of cancer dynamics and paving the way for tailored therapeutic interventions.

Indexed as

Biomarkers, TumorCarcinoma, Non-Small-Cell LungLeukapheresisLung NeoplasmsNeoplastic Cells, CirculatingPhenotypeCell Line, TumorEpithelial-Mesenchymal TransitionGene Expression ProfilingHumansSingle-Cell AnalysisTranscriptomeBiomarkers, TumorCirculating tumor cellsIntratumor heterogeneityNon-small cell lung cancerSingle cell RNA sequencing

Identifiers

PMID38720314
PMCPMC11077784

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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.