Research Paper Volume 13, Issue 11 pp 14590—14603

Prevalence of proliferating CD8+ cells in normal lymphatic tissues, inflammation and cancer

Niclas C. Blessin1, *, , Raed Abu-Hashem1, *, , Tim Mandelkow1, , Wenchao Li1, , Ronald Simon1, , Claudia Hube-Magg1, , Christina Möller-Koop1, , Melanie Witt1, , Alice Schmidt1, , Franziska Büscheck1, , Christoph Fraune1, , Andreas M. Luebke1, , Katharina Möller1, , Frank Jacobsen1, , Florian Lutz1, , Maximilian Lennartz1, , Stefan Steurer1, , Guido Sauter1, , Doris Höflmayer1, , Maria Christina Tsourlakis1, , Andrea Hinsch1, , Eike Burandt1, , Waldemar Wilczak1, , Sarah Minner1, , Till S. Clauditz1, ,

  • 1 Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg D-20246, Germany
* Equal contribution

Received: October 14, 2020       Accepted: May 11, 2021       Published: June 3, 2021
How to Cite

Copyright: © 2021 Blessin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


CD8+ cytotoxic T-lymphocytes are essential components of the anti-tumor immunity. To better understand the expansion of CD8+ T-cells we used multiplex fluorescence immunohistochemistry to study Ki67+CD8+ cells in normal lymphoid tissues, selected inflammatory diseases and cancers in 41 large sections/ microenvironment tissue microarrays (TMAs) as well as 765 samples in a conventional TMA format. The evaluation of more than 20 different compartments of normal lymphoid tissues revealed that the percentage of proliferating (ki67+) CD8+ cells did commonly not exceed 3%. In inflammations, the percentage of Ki67+CD8+ cells was more variable and higher compared to normal tissues. In cancers, the percentage of Ki67+CD8+ cells was higher in the tumor center than at the invasive margin. In the tumor center of 765 colorectal cancers, the density of Ki67+CD8+ cells and the percentage of proliferating CD8+ cytotoxic T-cells was significantly associated with microsatellite instability (p<0.0001), pT (p<0.0002) and pN category (p<0.0098). In summary, these data show that the percentage of Ki67+CD8+ cells is usually at a baseline proliferation rate below 3% in healthy secondary lymphoid organs. This rate is often markedly higher in inflammatory and neoplastic diseases compared to normal tissues. The striking link with unfavorable tumor features in colorectal cancer suggest a potential clinical utility of assessing the percentage of Ki67+CD8+ cells to predict patients outcome.


CRC: colorectal cancer; IHC: immunohistochemistry; MSI: microsatellite instability; SD: standard deviation; pN: pathological nodal stage; pT: pathological tumor stage; TILs: tumor infiltrating lymphocytes; TMA: tissue microarray.