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.