Evidence map›Paper›PMID 40210237›Full record

ArticleJournal for immunotherapy of cancer2025

Prior chemotherapy deteriorates T-cell quality for CAR T-cell therapy in B-cell non-Hodgkin's lymphoma.

Charlotte Herzberg, Phillip Schiele, Anna Luzie Walter, Frederik Hamm, Benedikt Obermayer, Jonas Kath, David Busch, Andrea Stroux, Mareike Frick, Olaf Penack and 7 more

Erratum issuedAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Review
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  7. Phase 1 Study of KITE-222, an Autologous CLL-1-Directed CAR T-cell Therapy in Patients with Relapsed/Refractory Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  8. Article
  9. Review
  10. Review
  11. Naïve CD4Nature communications · 2026
    Article
  12. Article
  13. Adoptive T-cell therapies in the clinic.Bioengineering & translational medicine · 2026
    Review
  14. Review
  15. CAR-T cell immunotherapy in rhabdomyosarcoma.Journal of translational medicine · 2026
    Review
  16. Article
  17. Review
  18. Review
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  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Charlotte HerzbergBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.ORCID http://orcid.org/0009-0005-7401-6421
Phillip SchieleBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.ORCID http://orcid.org/0000-0002-2342-3597
Anna Luzie WalterBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.
Frederik HammBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.
Benedikt ObermayerBerlin Institute of Health at Charité, Universitätsmedizin Berlin, Core Unit Bioinformatics, Berlin, Germany.
Jonas KathBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.
David BuschDepartment of Hematology, Oncology and Tumor Immunology, Charité University Hospital Berlin, Berlin, Germany.
Andrea StrouxInstitute for Biometrie and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Mareike FrickDepartment of Hematology, Oncology and Tumor Immunology, Charité University Hospital Berlin, Berlin, Germany.
Olaf PenackDepartment of Hematology, Oncology and Tumor Immunology, Charité University Hospital Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-4876-802X
Frederik DammDepartment of Hematology, Oncology and Tumor Immunology, Charité University Hospital Berlin, Berlin, Germany.
Dimitrios L WagnerBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.
Julia PolanskyBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.
Lars BullingerBSIO Berlin School of Integrative Oncology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Annette KünkeleBSIO Berlin School of Integrative Oncology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-8406-5412
Marco FrentschBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.
Il-Kang NaBerlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany il-kang.na@bih-charite.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChimeric antigen receptor (CAR) T-cell therapy depends on T cells that are genetically modified to recognize and attack cancer cells. Their effectiveness thus hinges on the functionality of a patient's own T cells. Since CAR T-cell therapy is currently only approved for advanced cancers after at least one line of chemotherapy, we evaluated the potential negative effects of prior exposure to chemotherapy on T-cell functionality.

methodsWe studied T cells of two B-cell non-Hodgkin's lymphoma patient cohorts, one collected before treatment (pre-therapy) and the other after one or more (median 3) lines of chemotherapy (post-therapy). Leveraging advanced multiparameter flow cytometry, single-cell RNA sequencing (scRNA-seq), whole-genome DNA methylation arrays and in vitro functionality testing of generated CAR T cells, we compared patient samples in their suitability for effective CAR T-cell therapy.

resultsWe discovered significant modifications in T-cell subsets and their transcriptional profiles secondary to chemotherapy exposure. Our analysis revealed a discernible shift towards phenotypically more differentiated T cells and an upregulation of markers indicative of T-cell exhaustion. Additionally, scRNA-seq and DNA methylation analyses revealed gene expression and epigenetic changes associated with diminished functionality in post-therapy T cells. Cytotoxicity assays demonstrated superior killing efficacy of CAR T cells derived from treatment-naïve patients compared with those with chemotherapy history.

conclusionsThese findings corroborate that employing T cells collected prior to frontline chemotherapy could enhance the effectiveness of CAR T-cell therapy and improve patient outcomes.

Indexed as

Immunotherapy, AdoptiveLymphoma, B-CellReceptors, Chimeric AntigenT-LymphocytesDNA MethylationFemaleHumansMaleReceptors, Chimeric AntigenAdoptive cell therapy - ACTChimeric antigen receptor - CARLymphoma

Identifiers

PMID40210237
PMCPMC11987159

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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.