% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Rhle:182606,
      author       = {A. Rühle$^*$ and J. Todorovic and S. S. K. Spohn$^*$ and
                      E. Gkika$^*$ and C. Becker and A. Knopf and C. Zamboglou$^*$
                      and T. Sprave$^*$ and M. Werner and A.-L. Grosu$^*$ and G.
                      Kayser and N. Nicolay$^*$},
      title        = {{P}rognostic value of tumor-infiltrating immune cells and
                      immune checkpoints in elderly head-and-neck squamous cell
                      carcinoma patients undergoing definitive
                      (chemo)radiotherapy.},
      journal      = {Radiation oncology},
      volume       = {17},
      number       = {1},
      issn         = {1748-717X},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2022-02787},
      pages        = {181},
      year         = {2022},
      note         = {#EA:E055#LA:E055#},
      abstract     = {Tumor-infiltrating lymphocytes (TILs) are associated with
                      locoregional control (LRC) in head-and-neck squamous cell
                      carcinoma (HNSCC) patients undergoing (chemo)radiotherapy.
                      As immunosenescence results in reduced immune activity, the
                      role of TILs in elderly HNSCC patients may differ compared
                      to younger patients, providing a rationale to study the
                      prognostic role of TILs and immune checkpoints (ICs) in this
                      population.Sixty-three HNSCC patients aged ≥ 65 years
                      undergoing definitive (chemo)radiotherapy between 2010 and
                      2019 with sufficient material from pre-treatment biopsies
                      were included in the analysis. Immunohistochemical stainings
                      of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of
                      osteopontin as an immunosenescence-associated protein were
                      performed. Overall survival (OS) and progression-free
                      survival (PFS) were determined using the Kaplan-Meier
                      method, and Fine-Gray's models were used for locoregional
                      failure (LRF) analyses.While there was no correlation
                      between patient age and IC expression, osteopontin levels
                      correlated with increasing age (r = 0.322, p < 0.05).
                      Two-year OS, PFS, and LRC were $44\%,$ $34\%,$ and $71\%,$
                      respectively. Increased LAG3 expression, both
                      intraepithelial (SHR = 0.33, p < 0.05) and stromal (SHR =
                      0.38, p < 0.05), and elevated stromal TIM3 expression (SHR =
                      0.32, p < 0.05) corresponded with reduced LRFs. Absent
                      tumoral PD-L1 expression (TPS = $0\%)$ was associated with
                      more LRFs (SHR = 0.28, p < 0.05). There was a trend towards
                      improved LRF rates in elderly patients with increased
                      intraepithelial CD3 + (SHR = 0.52, p = 0.07) and CD8 + (SHR
                      = 0.52, p = 0.09) TIL levels.LAG3, TIM3 and TPS are
                      promising biomarkers in elderly HNSCC patients receiving
                      (chemo)radiotherapy. Considering the frequency of non-cancer
                      related deaths in this population, the prognostic value of
                      these biomarkers primarily relates to LRC.},
      keywords     = {Elderly (Other) / Geriatric (Other) / Head-and-neck cancer
                      (Other) / Immune checkpoint (Other) / Immunosenescence
                      (Other) / Radiotherapy (Other) / Tumor-infiltrating
                      lymphocytes (Other)},
      cin          = {E055 / FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)E055-20160331 / I:(DE-He78)FR01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36376922},
      doi          = {10.1186/s13014-022-02153-9},
      url          = {https://inrepo02.dkfz.de/record/182606},
}