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@ARTICLE{Steen:285669,
      author       = {S. Steen and K. Semmelmayer and C. Flechtenmacher and J.
                      Hoffmann and K. Freier and D. Horn and J. Hess$^*$ and C.
                      Freudlsperger and J. Moratin},
      title        = {{D}ynamic {U}p-{R}egulation of {PD}-{L}1 in the
                      {P}rogression of {O}ral {S}quamous {C}ell {C}arcinoma.},
      journal      = {International journal of molecular sciences},
      volume       = {24},
      number       = {22},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DKFZ-2023-02492},
      pages        = {16386},
      year         = {2023},
      abstract     = {The introduction of immune checkpoint inhibition for
                      recurrent and metastatic head and neck cancer has brought a
                      new treatment option for patients suffering from advanced
                      oral cancers without a chance for curation using surgery or
                      radiotherapy. The application of immune checkpoint
                      inhibitors in most cases is based on the expression levels
                      of PD-L1 in the tumor tissue. To date, there is a lack of
                      data on the dynamic regulation of PD-L1 during disease
                      progression. Therefore, this study aimed to evaluate the
                      expression levels of PD-L1 in a large cohort of patients (n
                      = 222) with oral squamous cell carcinoma including primary
                      and recurrent tumors. Semiautomatic digital pathology
                      scoring was used for the assessment of PD-L1 expression
                      levels in primary and recurrent oral squamous cell
                      carcinoma. Survival analysis was performed to evaluate the
                      prognostic significance of the protein expression at
                      different stages of the disease. We found a significant
                      up-regulation of PD-L1 expression from primary disease to
                      recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1
                      ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In
                      several cases, a shift from low PD-L1 expression in primary
                      tumors to high PD-L1 expression in recurrent tumors was
                      identified. Multivariate Cox regression analysis did not
                      reveal a significantly higher risk of death (p = 0.078) or
                      recurrence (p = 0.926) in patients with higher PD-L1
                      expression. Our findings indicate that the exclusive
                      analysis of primary tumor tissue prior to the application of
                      checkpoint blockade may lead to the misjudgment of PD-L1
                      expression in recurrent tumors.},
      keywords     = {Humans / Squamous Cell Carcinoma of Head and Neck /
                      Carcinoma, Squamous Cell: pathology / B7-H1 Antigen:
                      metabolism / Up-Regulation / Mouth Neoplasms: genetics /
                      Neoplasm Recurrence, Local: genetics / Head and Neck
                      Neoplasms / HNSCC (Other) / PD-L1 (Other) / immune
                      checkpoint inhibitor (Other) / metastases (Other) / oral
                      cancer (Other) / recurrence (Other) / B7-H1 Antigen (NLM
                      Chemicals)},
      cin          = {E221},
      ddc          = {540},
      cid          = {I:(DE-He78)E221-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38003576},
      pmc          = {pmc:PMC10671831},
      doi          = {10.3390/ijms242216386},
      url          = {https://inrepo02.dkfz.de/record/285669},
}