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@ARTICLE{Yousuf:276389,
      author       = {S. Yousuf and M. Qiu and L. V. v. Voithenberg$^*$ and J.
                      Hulkkonen and I. Macinkovic and A. R. Schulz and D. Hartmann
                      and F. Mueller$^*$ and M. Mijatovic and D. Ibberson and K.
                      T. AlHalabi and J. Hetzer$^*$ and S. Anders and B.
                      Brüne$^*$ and H. E. Mei and C. D. Imbusch$^*$ and B.
                      Brors$^*$ and M. Heikenwälder$^*$ and M. M. Gaida and M. W.
                      Büchler and A. Weigert$^*$ and T. Hackert and S. Roth},
      title        = {{S}patially resolved multi-omics single-cell analyses
                      inform mechanisms of immune-dysfunction in pancreatic
                      cancer.},
      journal      = {Gastroenterology},
      volume       = {165},
      number       = {4},
      issn         = {0016-5085},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {Saunders},
      reportid     = {DKFZ-2023-01086},
      pages        = {891-908.e14},
      year         = {2023},
      note         = {2023 Oct;165(4):891-908.e14},
      abstract     = {As pancreatic ductal adenocarcinoma (PDAC) continues to be
                      recalcitrant to therapeutic interventions including poor
                      response to immunotherapy, albeit effective in other solid
                      malignancies, a more nuanced understanding of the immune
                      microenvironment in PDAC is urgently needed. We aimed to
                      unveil a detailed view of the immune micromilieu in PDAC
                      using a spatially-resolved multimodal single cell
                      approach.We applied single cell RNA sequencing, spatial
                      transcriptomics, multiplex immunohistochemistry and mass
                      cytometry to profile the immune compartment in treatment
                      naive PDAC tumors and matched adjacent normal pancreatic
                      tissue, as well as in the systemic circulation. We
                      determined prognostic associations of immune signatures, and
                      performed a meta-analysis of the immune microenvironment in
                      PDAC and lung adenocarcinoma (LUAD) on single-cell level.We
                      provide a spatially-resolved fine map of the immune
                      landscape in PDAC. We substantiate the exhausted phenotype
                      of CD8 T cells and immunosuppressive features of myeloid
                      cells, and highlight immune subsets with potentially
                      underappreciated roles in PDAC, that diverge from immune
                      populations within adjacent normal areas, particularly CD4 T
                      cell subsets and NKT cells that are terminally exhausted and
                      acquire a regulatory phenotype. Differential analysis of
                      immune phenotypes in PDAC and LUAD revealed the presence of
                      extraordinarily immunosuppressive subtypes in PDAC, along
                      with a distinctive immune checkpoint composition.Our study
                      sheds light on the multilayered immune dysfunction in PDAC
                      and presents a holistic view of the immune landscape in PDAC
                      and LUAD, providing a comprehensive resource for functional
                      studies and the exploration of therapeutically actionable
                      targets in PDAC.},
      keywords     = {lung cancer (Other) / pancreatic cancer (Other) / single
                      cell multi-omics (Other) / tumor immunology (Other)},
      cin          = {B330 / F180 / FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)B330-20160331 / I:(DE-He78)F180-20160331 /
                      I:(DE-He78)FM01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37263303},
      doi          = {10.1053/j.gastro.2023.05.036},
      url          = {https://inrepo02.dkfz.de/record/276389},
}