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@ARTICLE{Schuch:141188,
      author       = {A. Schuch and B. F. Zecher and P. A. Müller and M. P.
                      Correia$^*$ and F. Daul and C. Rennert and C. Tauber and K.
                      Schlitt and T. Boettler and C. Neumann-Haefelin and H.
                      Hengel and H. Pircher and A. Cerwenka$^*$ and R. Thimme and
                      M. Hofmann},
      title        = {{NK}-cell responses are biased towards {CD}16-mediated
                      effector functions in chronic {H}epatitis {B} virus
                      infection.},
      journal      = {Journal of hepatology},
      volume       = {70},
      number       = {3},
      issn         = {0168-8278},
      address      = {[S.l.]},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2018-01711},
      pages        = {351-360},
      year         = {2019},
      abstract     = {Phenotypical and functional NK-cell alterations are well
                      described in chronic Hepatitis B virus (cHBV) infection.
                      However, it is largely unknown whether these alterations
                      result from general effects on the overall NK-cell
                      population or the emergence of distinct NK-cell subsets.
                      Indeed, memory-like NK cells emerge in association with
                      human cytomegalovirus (HCMV) infection that is common in
                      cHBV infection. These memory-like NK cells display an
                      altered phenotype and functionality including superior
                      CD16-mediated effector functions.To assess the impact of
                      memory-like NK cells on phenotypic and functional
                      alterations in cHBV infection we performed in-depth analyses
                      of circulating NK cells in 52 cHBV patients, 45 chronically
                      HCV-infected patients and 50 healthy donors (HD) with
                      respect to their HCMV serostatus.In cHBV/HCMV+ patients,
                      FcεRIγ- memory-like NK cells were present in higher
                      frequencies and with higher prevalence compared to HD/HCMV+.
                      This pronounced HCMV-associated memory-like NK-cell
                      expansion could be identified as key determinant of the
                      NK-cell response in cHBV infection. Furthermore, we observed
                      that memory-like NK cells consist of epigenetically distinct
                      subsets and exhibit metabolic key characteristics of
                      long-living cells. Despite ongoing chronic infection, the
                      phenotype of memory-like NK cells was conserved in
                      cHBV/HCMV+ patients. Functional characteristics of
                      memory-like NK cells also remained largely unaffected by
                      cHBV infection with the exception of an increased
                      degranulation capacity in response to CD16 stimulation that
                      was, however, detectable in both, memory-like and
                      conventional NK cells.The emergence of HCMV-associated
                      memory-like NK cells shapes the overall NK-cell response in
                      cHBV infection and contributes to a general shift towards
                      CD16-mediated effector functions. HCMV coinfection therefore
                      needs to be considered with respect to the design of
                      immunotherapeutic approaches in HBV cure targeting NK
                      cells.In chronic hepatitis B virus infection, the NK-cell
                      phenotype and function is altered in comparison to healthy
                      donors. In this study, we demonstrate that this is linked to
                      the emergence of a distinct NK-cell subset, namely
                      memory-like NK cells. The emergence of these memory-like NK
                      cells is associated with co-infection of human
                      cytomegalovirus that affects the majority of patients with
                      chronic hepatitis B.},
      cin          = {D080},
      ddc          = {610},
      cid          = {I:(DE-He78)D080-20160331},
      pnm          = {314 - Tumor immunology (POF3-314)},
      pid          = {G:(DE-HGF)POF3-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30342116},
      doi          = {10.1016/j.jhep.2018.10.006},
      url          = {https://inrepo02.dkfz.de/record/141188},
}