Background Expansion of CD8⁺ cytotoxic T lymphocytes is a prerequisite for anti-cancer immune activity. In the era of immune checkpoint therapy, profound knowledge of the dynamics of CD8⁺ has regained considerable interest. However, systematically acquired data on CD8⁺ proliferation in large sets of normal and diseased tissues are sparse.

Materials and Methods Here, we applied multiplex fluorescence immunohistochemistry to conventional large sections and tissue microarrays in order to quantitate Ki67⁺CD8⁺ cells in >20 different compartments of normal lymphoid tissues, 7 types of inflammatory diseases and 785 cancers.

Results In most normal lymphoid tissues (tonsil, lymph node, thymus, Peyer’s patches, spleen, colon, appendix) the percentage of Ki67⁺CD8⁺ cells typically did not exceed 3%. The percentage of Ki67⁺CD8⁺ cells was markedly higher (45%) in the immune-active cortex of the thymus, however. In inflammatory conditions (including Hashimoto thyroiditis, Lichen sclerosus of the penis, sarcoidosis, sialadenitis, IgG4 pancreatitis, Crohn’s disease and eczema), the percentage of Ki67⁺CD8⁺ cells was much more variable and often sharply higher than in normal tissues. It ranged from 0.5% in one patient with sialadenitis to 19% in the intraepithelial compartment of Crohn’s disease. In 765 colorectal cancers, the fraction of Ki67 positive CD8⁺ cytotoxic T cells ranged from 0 to 100% (mean: 20.6%). A high fraction of Ki67⁺CD8⁺ cells was significantly associated with microsatellite instability (p<0.0001), low pT stage (p<0.0001) and absence of nodal metastases (p=0.0005).

Conclusions In summary, our data show a variable increase of the fraction of proliferating CD8⁺ T cells in cancers and in inflammatory diseases as compared to healthy secondary lymphoid organs. The striking link with microsatellite instability and unfavorable tumor features suggest a potential clinical utility of assessing Ki67⁺CD8⁺ in colorectal cancer.

Disclosure Information K. Möller: None. M. Lennartz: None. R. Abu-Hashem: None. N.C. Blessin: None. T. Mandelkow: None. E. Bady: None. C. Hube-Magg: None. R. Simon: None. G. Sauter: None. C. Fraune: None. T.S. Clauditz: None. F. Büscheck: None. A.M. Luebke: None.