Prognostic role of proliferating CD8+ cytotoxic Tcells in human cancers
Niclas C. Blessin, Wenchao Li, Tim Mandelkow, Hannah L. Jansen, Cheng Yang, Jonas B. Raedler, Ronald Simon, Franziska Büscheck, David Dum, Andreas M. Luebke, Andrea Hinsch, Katharina Möller, Anne Menz, Christian Bernreuther, Patrick Lebok, Till S. Clauditz, Guido Sauter, Andreas H. Marx, Ria Uhlig, Waldemar Wilczak, Sarah Minner, Till Krech, Christoph Fraune, Doris Höflmayer, Eike Burandt, Stefan Steurer
Abstract
Abstract 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.