Prognostic role of proliferating CD8+ cytotoxic Tcells in human cancers

Cell Oncol (Dordr). 2021 Aug;44(4):793-803. doi: 10.1007/s13402-021-00601-4. Epub 2021 Apr 17.

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.

Keywords: Breast cancer; CD8+ cytotoxic Tcells; Colorectal cancer; Gastric cancer; Ovarian cancer; Pancreatic cancer; Renal cell cancer; Tumor microenvironment.

MeSH terms

  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Proliferation*
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Neoplasm Staging
  • Neoplasms / classification
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Prognosis
  • Survival Analysis
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Cytotoxic / pathology

Substances

  • Ki-67 Antigen