Apoptosis of immune cells in the tumor microenvironment and peripheral circulation of patients with cancer: implications for immunotherapy.
Rapid turnover of lymphocytes observed in patients with cancer appears to be driven by increased apoptosis of T lymphocytes or insufficient thymic output of recent thymic emigrants (RTE). Using multicolor flow cytometry and apoptosis assays, we found that CD8+CD95+Annexin+ T cells are dying at a rate that is significantly higher in patients with cancer than in normal controls (NC). CD8+ effector subsets of T cells were particularly vulnerable to apoptosis. Thymic excision circle (TREC) analysis of peripheral blood lymphocytes showed a decreased number of RTE in these patients. Together, the data suggest that a high rate of T-cell turnover might contribute to immunologic imbalance in patients with cancer and have unfavorable effects on immunotherapy, including therapeutic antitumor vaccines.
Whiteside
Theresa L
TL
University of Pittsburgh Cancer Institute, 200 Lothrop Street, BST 211, W1041, Pittsburgh, PA 15213-2582, USA. whitesidet@msx.upmc.edu
D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy