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@ARTICLE{Alwers:182763,
      author       = {E. Alwers$^*$ and J. N. Kather and M. Kloor$^*$ and A.
                      Brobeil and K. E. Tagscherer and W. Roth and A. Echle and E.
                      Amitay$^*$ and J. Chang-Claude$^*$ and H. Brenner$^*$ and M.
                      Hoffmeister$^*$},
      title        = {{V}alidation of the prognostic value of {CD}3 and {CD}8
                      cell densities analogous to the {I}mmunoscore® by stage and
                      location of colorectal cancer: an independent patient cohort
                      study.},
      journal      = {The journal of pathology: clinical research},
      volume       = {9},
      number       = {2},
      issn         = {2056-4538},
      address      = {Chichester},
      publisher    = {Wiley},
      reportid     = {DKFZ-2022-02903},
      pages        = {129-136},
      year         = {2023},
      note         = {#EA:C070#LA:C070# / 2023 Mar;9(2):129-136},
      abstract     = {In addition to the traditional staging system in colorectal
                      cancer (CRC), the Immunoscore® has been proposed to
                      characterize the level of immune infiltration in tumor
                      tissue and as a potential prognostic marker. The aim of this
                      study was to examine and validate associations of an immune
                      cell score analogous to the Immunoscore® with established
                      molecular tumor markers and with CRC patient survival in a
                      routine setting. Patients from a population-based cohort
                      study with available CRC tumor tissue blocks were included
                      in this analysis. CD3+ and CD8+ tumor infiltrating
                      lymphocytes in the tumor center and invasive margin were
                      determined in stained tumor tissue slides. Based on the
                      T-cell density in each region, an immune cell score closely
                      analogous to the concept of the Immunoscore® was calculated
                      and tumors categorized into IS-low, IS-intermediate, or
                      IS-high. Logistic regression models were used to assess
                      associations between clinicopathological characteristics
                      with the immune cell score, and Cox proportional hazards
                      models to analyze associations with cancer-specific,
                      relapse-free, and overall survival. From 1,535 patients with
                      CRC, 411 $(27\%)$ had IS-high tumors. Microsatellite
                      instability (MSI-high) was strongly associated with higher
                      immune cell score levels (p < 0.001). Stage I-III patients
                      with IS-high had better CRC-specific and relapse-free
                      survival compared to patients with IS-low (hazard ratio [HR]
                      = 0.42 [0.27-0.66] and HR = 0.45 [0.31-0.67], respectively).
                      Patients with microsatellite stable (MSS) tumors and IS-high
                      had better survival (HRCSS = 0.60 [0.42-0.88]) compared to
                      MSS/IS-low patients. In this population-based cohort of CRC
                      patients, the immune cell score was significantly associated
                      with better patient survival. It was a similarly strong
                      prognostic marker in patients with MSI-high tumors and in
                      the larger group of patients with MSS tumors. Additionally,
                      this study showed that it is possible to implement an
                      analogous immune cell score approach and validate the
                      Immunoscore® using open source software in an academic
                      setting. Thus, the Immunoscore® could be useful to improve
                      the traditional staging system in colon and rectal cancer
                      used in clinical practice.},
      keywords     = {colorectal cancer (Other) / immune infiltration (Other) /
                      microsatellite instability (Other) / survival (Other)},
      cin          = {C070 / F210 / C020 / HD01 / C120},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)F210-20160331 /
                      I:(DE-He78)C020-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)C120-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36424650},
      doi          = {10.1002/cjp2.304},
      url          = {https://inrepo02.dkfz.de/record/182763},
}