Abstract 4979: Prevalence of proliferating CD8+cells in normal lymphatic tissues, inflammation and cancer

Abstract

Abstract 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. 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. 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). 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. Citation Format: Maximilian Lennartz, Raed Abu-Hashem, Niclas Christian Blessin, Tim Mandelkow, Elena Bady, Ronald Simon, Claudia Hube-Magg, Guido Sauter, Christoph Fraune, Katharina Möller, Till S. Clauditz, Andreas M. Luebke, Franziska Büscheck. Prevalence of proliferating CD8+cells in normal lymphatic tissues, inflammation and cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4979.