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@ARTICLE{Delvecchio:157917,
      author       = {Delvecchio and Fincham and Spear and Clear and
                      Roy-Luzarraga and Balkwill and Gribben and Bombardieri and
                      Hodivala-Dilke and Capasso, Melania and Kocher},
      title        = {{P}ancreatic {C}ancer {C}hemotherapy {I}s {P}otentiated by
                      {I}nduction of {T}ertiary {L}ymphoid {S}tructures in {M}ice},
      journal      = {Cellular and Molecular Gastroenterology and Hepatology},
      volume       = {12},
      number       = {5},
      issn         = {2352-345X},
      address      = {New York, NY},
      publisher    = {Elsevier},
      reportid     = {DZNE-2021-01291},
      pages        = {1543-1565},
      year         = {2021},
      note         = {CC BY},
      abstract     = {Background and aims: The presence of tertiary lymphoid
                      structures (TLSs) may confer survival benefit to patients
                      with pancreatic ductal adenocarcinoma (PDAC), in an
                      otherwise immunologically inert malignancy. Yet, the precise
                      role in PDAC has not been elucidated. Here, we aim to
                      investigate the structure and role of TLSs in human and
                      murine pancreatic cancer.Methods: Multicolor
                      immunofluorescence and immunohistochemistry were used to
                      fully characterize TLSs in human and murine (transgenic [KPC
                      (KrasG12D, p53R172H, Pdx-1-Cre)] and orthotopic) pancreatic
                      cancer. An orthotopic murine model was developed to study
                      the development of TLSs and the effect of the combined
                      chemotherapy and immunotherapy on tumor growth.Results:
                      Mature, functional TLSs are not ubiquitous in human PDAC and
                      KPC murine cancers and are absent in the orthotopic murine
                      model. TLS formation can be induced in the orthotopic model
                      of PDAC after intratumoral injection of lymphoid chemokines
                      (CXCL13/CCL21). Coadministration of systemic chemotherapy
                      (gemcitabine) and intratumoral lymphoid chemokines into
                      orthotopic tumors altered immune cell infiltration
                      ,facilitating TLS induction and potentiating antitumor
                      activity of chemotherapy. This resulted in significant tumor
                      reduction, an effect not achieved by either treatment alone.
                      Antitumor activity seen after TLS induction is associated
                      with B cell-mediated dendritic cell activation.Conclusions:
                      This study provides supportive evidence that TLS induction
                      may potentiate the antitumor activity of chemotherapy in a
                      murine model of PDAC. A detailed understanding of TLS
                      kinetics and their induction, owing to multiple host and
                      tumor factors, may help design personalized therapies
                      harnessing the potential of immune-oncology.},
      keywords     = {Animals / Antigen Presentation / Antineoplastic Agents:
                      pharmacology / Antineoplastic Agents: therapeutic use /
                      B-Lymphocytes: immunology / B-Lymphocytes: metabolism /
                      B-Lymphocytes: pathology / Biomarkers / Carcinoma,
                      Pancreatic Ductal: drug therapy / Carcinoma, Pancreatic
                      Ductal: immunology / Carcinoma, Pancreatic Ductal:
                      metabolism / Carcinoma, Pancreatic Ductal: pathology / Cell
                      Line, Tumor / Cytokines: metabolism / Dendritic Cells:
                      immunology / Dendritic Cells: metabolism / Disease Models,
                      Animal / Germinal Center / Humans / Immunohistochemistry /
                      Mice / Mice, Transgenic / Pancreatic Neoplasms: drug therapy
                      / Pancreatic Neoplasms: immunology / Pancreatic Neoplasms:
                      metabolism / Pancreatic Neoplasms: pathology /
                      T-Lymphocytes: immunology / T-Lymphocytes: metabolism /
                      T-Lymphocytes: pathology / Tertiary Lymphoid Structures:
                      drug therapy / Tertiary Lymphoid Structures: immunology /
                      Tertiary Lymphoid Structures: pathology / Treatment Outcome
                      / Tumor Microenvironment: drug effects / Tumor
                      Microenvironment: immunology / Xenograft Model Antitumor
                      Assays},
      cin          = {AG Capasso},
      ddc          = {610},
      cid          = {I:(DE-2719)1013033},
      pnm          = {351 - Brain Function (POF4-351) / EXC
                      2151: ImmunoSensation2 - the immune sensory system
                      (390873048)},
      pid          = {G:(DE-HGF)POF4-351 / G:(GEPRIS)390873048},
      experiment   = {EXP:(DE-2719)LMF-20190308},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC8529396},
      pubmed       = {pmid:34252585},
      doi          = {10.1016/j.jcmgh.2021.06.023},
      url          = {https://pub.dzne.de/record/157917},
}