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

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 Ki67CD8 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 Ki67CD8 cells was more variable and higher compared to normal tissues. In cancers, the percentage of Ki67CD8 cells was higher in the tumor center than at the invasive margin. In the tumor center of 765 colorectal cancers, the density of Ki67CD8 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 Ki67CD8 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 Ki67CD8 cells to predict patients outcome.