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@ARTICLE{Poschke:130346,
      author       = {I. Poschke$^*$ and M. Faryna and F. Bergmann and M.
                      Flossdorf$^*$ and C. Lauenstein$^*$ and J. Hermes$^*$ and U.
                      Hinz and T. Hank and R. Ehrenberg and M. Volkmar$^*$ and M.
                      Loewer and H. Glimm and T. Hackert and M. Sprick$^*$ and T.
                      Höfer$^*$ and A. Trumpp$^*$ and N. Halama and J. C. Hassel
                      and O. Strobel$^*$ and M. Büchler and U. Sahin and R.
                      Offringa$^*$},
      title        = {{I}dentification of a tumor-reactive {T}-cell repertoire in
                      the immune infiltrate of patients with resectable pancreatic
                      ductal adenocarcinoma.},
      journal      = {OncoImmunology},
      volume       = {5},
      number       = {12},
      issn         = {2162-402X},
      address      = {Austin, Tex.},
      publisher    = {Landes Bioscience},
      reportid     = {DKFZ-2017-05425},
      pages        = {e1240859 -},
      year         = {2016},
      abstract     = {The devastating prognosis of patients with resectable
                      pancreatic ductal adenocarcinoma (PDA) presents an urgent
                      need for the development of therapeutic strategies targeting
                      disseminated tumor cells. Until now, T-cell therapy has been
                      scarcely pursued in PDA, due to the prevailing view that it
                      represents a poorly immunogenic tumor.We systematically
                      analyzed T-cell infiltrates in tumor biopsies from 127
                      patients with resectable PDA by means of
                      immunohistochemistry, flow cytometry, T-cell receptor (TCR)
                      deep-sequencing and functional analysis of in vitro expanded
                      T-cell cultures. Parallel studies were performed on
                      tumor-infiltrating lymphocytes (TIL) from 44 patients with
                      metastatic melanoma.Prominent T-cell infiltrates, as well as
                      tertiary lymphoid structures harboring proliferating
                      T-cells, were detected in the vast majority of biopsies from
                      PDA patients. The notion that the tumor is a site of local
                      T-cell expansion was strengthened by TCR deep-sequencing,
                      revealing that the T-cell repertoire in the tumor is
                      dominated by highly frequent CDR3 sequences that can be up
                      to 10,000-fold enriched in tumor as compared to peripheral
                      blood. In fact, TCR repertoire composition in PDA resembled
                      that in melanoma. Moreover, in vitro expansion of TILs was
                      equally efficient for PDA and melanoma, resulting in T-cell
                      cultures displaying HLA class I-restricted reactivity
                      against autologous tumor cells.The tumor-infiltrating T-cell
                      response in PDA shows striking similarity to that in
                      melanoma, where adoptive T-cell therapy has significant
                      therapeutic impact. Our findings indicate that T-cell-based
                      therapies may be used to counter disease recurrence in
                      patients with resectable PDA.},
      cin          = {G180 / B086},
      ddc          = {610},
      cid          = {I:(DE-He78)G180-20160331 / I:(DE-He78)B086-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28123878},
      pmc          = {pmc:PMC5215250},
      doi          = {10.1080/2162402X.2016.1240859},
      url          = {https://inrepo02.dkfz.de/record/130346},
}