Prognostic role of proliferating CD8+ cytotoxic Tcells in human cancers

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.

Automated summary

Expansion of CD8(+) cytotoxic T lymphocytes plays a crucial role in anti-cancer immune activity, with varying impact on tumor prognosis depending on the tumor type. In colorectal and renal cell cancer, proliferating CD8(+) T cells are associated with favorable tumor parameters and prolonged overall survival, while in breast, ovarian, pancreatic and gastric cancer their role is not linked to clinicopathological data.