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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&lt;0.0001), pT (p&lt;0.0002) and pN category (p&lt;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.

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