P03.06 Pattern of Ki67+expanding CD8+cytotoxic T cells in healthy tissues, inflammation and the cancer microenvironment. (1st October 2020)

• Record Type: Journal Article
• Authors: Möller, K; Lennartz, M; Abu-Hashem, R; Blessin, NC; Mandelkow, T; Bady, E; Hube-Magg, C; Simon, R; Sauter, G; Fraune, C; Clauditz, TS; Büscheck, F; Luebke, AM
• Is Part Of: Journal for immunotherapy of cancer. Volume 8(2020)Supplement 2
• Page Start: A24
• Page End: A25
• Publication Date: 2020-10-01
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-ITOC7.46
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : 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.