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Prognostic role of proliferating CD8+ cytotoxic Tcells in human cancers

Authors: Blessin, Niclas C.; Li, Wenchao; Mandelkow, Tim; Jansen, Hannah L.; Yang, Cheng; Raedler, Jonas B.; Simon, Ronald; Büscheck, Franziska; Dum, David; Luebke, Andreas M.; Hinsch, Andrea; Möller, Katharina; Menz, Anne; Bernreuther, Christian; Lebok, Patrick; Clauditz, Till; Sauter, Guido; Marx, Andreas; Uhlig, Ria; Wilczak, Waldemar; Minner, Sarah; Krech, Till; Fraune, Christoph; Höflmayer, Doris; Burandt, Eike; Steurer, Stefan

Online: https://link.springer.com/10.1007/s13402-021-00601-4

Issue: Cell Oncol (Dordr) . 2021 Apr 17.


Purpose Expansion of CD8+ cytotoxic Tlymphocytes is a prerequisite for anti-cancer immune activity and has gained interest in the era of immune checkpoint therapy. Methods To understand the CD8+ T cell dynamics in the tumor microenvironment, we used multiplex fluorescence immunohistochemistry to quantitate CD8+ proliferation (Ki67 co-expression) in tissue microarrays from 1107 colorectal, 642 renal cell, 1066 breast, 375 ovarian, 451 pancreatic and 347 gastric cancer samples. Results The density and the percentage of proliferating (Ki67+) CD8+ T cells were both highly variable between tumor types as well as between patients with the same tumor type. Elevated density and percentage of proliferating CD8+ cytotoxic T cells were significantly associated with favorable tumor parameters such as low tumor stage, negative nodal stage (p ≤ 0.0041 each), prolonged overall survival (p ≤ 0.0028 each) and an inflamed immune phenotype (p = 0.0025) in colorectal cancer and, in contrast, linked to high tumor stage, advanced ISUP/Fuhrman/Thoenes grading (each p ≤ 0.003), shorter overall survival (p ≤ 0.0330 each) and an immune inflamed phenotype (p = 0.0094) in renal cell cancer. In breast, ovarian, pancreatic and gastric cancer the role of (Ki67+)CD8+ Tcells was not linked to clinicopathological data. Conclusion Our data demonstrate a tumor type dependent prognostic impact of proliferating (Ki67+)CD8+ Tcells and an inverse impact in colorectal and renal cell cancer.