@article{BoschertTeuschAljasemetal.2020,
  author    = {Boschert, Verena and Teusch, Jonas and Aljasem, Anwar and Schmucker, Philipp and Klenk, Nicola and Straub, Anton and Bittrich, Max and Seher, Axel and Linz, Christian and M{\"u}ller-Richter, Urs D. A. and Hartmann, Stefan},
  title     = {HGF-induced PD-L1 expression in head and neck cancer: preclinical and clinical findings},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {20},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21228770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236220},
  year      = {2020},
  abstract  = {Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal-epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient's sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.},
  language  = {en}
}