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@ARTICLE{Junkuhn:300323,
      author       = {C. Junkuhn and P. Schiele and A. L. Walter and F. Hamm and
                      B. Obermayer and D. Busch and A. Stroux and M. Frick and O.
                      Penack and F. Damm$^*$ and J. Polansky and L. Bullinger$^*$
                      and A. Künkele and M. Frentsch and I.-K. Na},
      title        = {{P}rior chemotherapy deteriorates {T}-cell quality for
                      {CAR} {T}-cell therapy in {B}-cell non-{H}odgkin's
                      lymphoma.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {13},
      number       = {4},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2025-00769},
      pages        = {e010709},
      year         = {2025},
      abstract     = {Chimeric 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.We 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.We 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.These findings corroborate that
                      employing T cells collected prior to frontline chemotherapy
                      could enhance the effectiveness of CAR T-cell therapy and
                      improve patient outcomes.},
      keywords     = {Humans / Immunotherapy, Adoptive: methods / T-Lymphocytes:
                      immunology / T-Lymphocytes: drug effects / Lymphoma, B-Cell:
                      therapy / Lymphoma, B-Cell: immunology / Lymphoma, B-Cell:
                      drug therapy / Receptors, Chimeric Antigen: metabolism / DNA
                      Methylation / Male / Female / Adoptive cell therapy - ACT
                      (Other) / Chimeric antigen receptor - CAR (Other) / Lymphoma
                      (Other) / Receptors, Chimeric Antigen (NLM Chemicals)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40210237},
      doi          = {10.1136/jitc-2024-010709},
      url          = {https://inrepo02.dkfz.de/record/300323},
}