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@ARTICLE{Klein:277442,
      author       = {S. Klein and A. Schulte and C. Arolt and Y. Tolkach and H.
                      C. Reinhardt$^*$ and R. Buettner and A. Quaas},
      title        = {{I}ntratumoral abundance of {M}2-macrophages is associated
                      with unfavorable prognosis and markers of {T}-cell
                      exhaustion in small cell lung cancer patients.},
      journal      = {Modern pathology},
      volume       = {36},
      number       = {10},
      issn         = {0893-3952},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2023-01379},
      pages        = {100272},
      year         = {2023},
      note         = {Volume 36, Issue 10, October 2023, 100272},
      abstract     = {Small cell lung cancer (SCLC) accounts for about $10-15\%$
                      of lung cancer cases. Unlike non-SCLC, therapy options for
                      SCLC are limited, reflected by a five-year survival rate of
                      about $7\%.$ At the same time, the rise of immunotherapeutic
                      approaches in cancer therapy has rationalized to account for
                      inflammatory phenotypes in tumors. However, the composition
                      of the inflammatory microenvironment in human SCLC is poorly
                      understood to date. In our study, we used in-depth image
                      analysis of virtual whole-slide-images of 45 SCLC tumors and
                      evaluated different markers of M2-macrophages (CD163, CD204)
                      together with global immunological markers (CD4, CD8, CD68,
                      CD38, FOXP3, CD20) and characterized their abundance
                      intratumorally using quantitative image analysis, combined
                      with a deep-learning model for tumor segmentation. In
                      addition, independent scoring, blinded to the results of the
                      computational analysis, was performed by an expert
                      pathologist of both CD163/CD204 and PD-L1. To this end, we
                      evaluated the prognostic relevance of the abundance of these
                      cell types to overall survival. Given a two-tier threshold
                      of the median of the M2 marker CD163 within the study
                      population, there was a 12 month overall survival rate of
                      $22\%$ $[95\%$ $CI=10-47\%]$ for patients with high CD163
                      abundance and $41\%$ $[95\%$ $CI=25-68\%]$ for patients with
                      low CD163 counts. Patients with increased CD163 had a median
                      overall survival of 3 months compared to 8.34 months for
                      patients with decreased CD163 counts (p=0.039) - which could
                      be confirmed by expert pathologist (p=0.018). By analyzing
                      cases with increased CD163 cell infiltrates, a trend for
                      higher FOXP3 counts and PD-L1 positive cells, together with
                      increased CD8 T-cell infiltrates were observed - which could
                      be confirmed using an independent cohort on transcriptional
                      level. Together, we showed that markers of M2 were
                      associated with unfavorable outcome in our study cohort.},
      keywords     = {CD163 (Other) / M2 (Other) / SCLC (Other) / Small cell lung
                      cancer (Other) / TME (Other) / biomarker (Other) / lung
                      cancer (Other) / macrophages (Other) / tumor
                      microenvironment (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37423586},
      doi          = {10.1016/j.modpat.2023.100272},
      url          = {https://inrepo02.dkfz.de/record/277442},
}