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@ARTICLE{deCoaa:120518,
      author       = {Y. P. de Coaña and M. Wolodarski and I. Poschke$^*$ and Y.
                      Yoshimoto and Y. Yang and M. Nyström and U. Edbäck and S.
                      E. Brage and A. Lundqvist and G. V. Masucci and J. Hansson
                      and R. Kiessling},
      title        = {{I}pilimumab treatment decreases monocytic {MDSC}s and
                      increases {CD}8 effector memory {T} cells in long-term
                      survivors with advanced melanoma.},
      journal      = {OncoTarget},
      volume       = {8},
      number       = {13},
      issn         = {1949-2553},
      address      = {[S.l.]},
      publisher    = {Impact Journals LLC},
      reportid     = {DKFZ-2017-00947},
      pages        = {21539-21553},
      year         = {2017},
      abstract     = {Ipilimumab has revolutionized malignant melanoma therapy,
                      but a better understanding of the mechanisms behind
                      treatment response and adverse effects is needed. In this
                      work, the immune system of ipilimumab treated patients was
                      monitored to investigate potential mechanisms of action that
                      may correlate with treatment outcome. Blood samples from 43
                      advanced melanoma patients were taken before, during and at
                      the end of treatment. Hematological parameters were measured
                      and flow cytometry analysis was performed in fresh samples
                      within two hours of sample collection. Strong differences in
                      markers CD45RA, CCR7, HLA-DR and CD15 between fresh and
                      cryopreserved samples were observed. Ipilimumab treatment
                      increased absolute lymphocyte counts, eosinophils, effector
                      T cells and their activation status, whilst diminishing the
                      suppressive side of the immune response, acting on
                      regulatory T cells and myeloid derived suppressor cells
                      (MDSCs). These effects were visible after one ipilimumab
                      infusion and, regarding eosinophil counts, correlated with
                      onset of adverse events. Monocytic MDSCs were decreased in
                      response to treatment only in patients with clinical
                      benefit; additionally, patients with a lower frequency of
                      these cells after the first ipilimumab infusion experienced
                      increased overall survival. CD8 effector memory T cell
                      frequencies at the end of treatment were higher in patients
                      with clinical benefit and positively correlated with
                      survival. These data show that a clinical response to
                      ipilimumab not only requires reshaping T cell populations,
                      but additionally involves a reduction in suppressive cells
                      such as monocytic MDSCs. Our work could provide insight on
                      predicting treatment outcome, assisting clinicians in
                      offering the best personalized therapeutic approach.},
      cin          = {G180},
      ddc          = {610},
      cid          = {I:(DE-He78)G180-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28423487},
      pmc          = {pmc:PMC5400604},
      doi          = {10.18632/oncotarget.15368},
      url          = {https://inrepo02.dkfz.de/record/120518},
}