Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Effect of irinotecan on the phenotype of peripheral blood leukocyte populations in patients with metastatic colorectal cancer

Abstract

BACKGROUND/AIMS: Previous studies have demonstrated a significant decrease in absolute numbers of CD3+CD4+, CD8+CD28+ and CD19+ lymphocytes, and an increase in the expression of activation markers on T-cells and the number of CD14+CD16+ monocytes in patients with metastatic cancer. Irinotecan (CPT-11) is now being widely used for treatment of metastatic colorectal cancer patients. METHODOLOGY: We have examined, by two-color flow cytometry, peripheral blood leukocyte populations before and during systemic treatment with CPT-11 in 14 patients with metastatic colorectal cancer. RESULTS: CD3+, CD3+CD4+, CD3+CD8+, CD8+CD28+ and CD19+ were significantly lower, and CD3+HLA-DR+ and CD14+CD16+ cells were higher in metastatic colorectal cancer patients compared to controls. After 2-4 months of CPT-11-based chemotherapy, significant increase in CD3+CD4+ cell numbers was observed in 8 patients who had initial CD3+CD4+ counts of less than 600 per microL (358 +/- 154 vs. 652 +/- 319 cells per microL, Wilcoxon test, P < 0.01), while in patients with higher initial CD3+CD4+ counts a trend for decrease was observed during therapy. A trend for an increase in CD8+CD28+ cell counts was observed in patients with low CD3+CD4+ numbers, but no other changes were observed during the treatment in other peripheral blood leukocyte populations examined. CONCLUSIONS: CD3+CD4+ lymphocytopenia, a decrease in CD8+CD28+ and CD19+ lymphocytes, increased expression of activation markers and CD14+CD16+ monocytosis are present in a significant proportion of metastatic colorectal cancer patients. CPT-11-based therapy seems to ameliorate CD3+CD4+ lymphocytopenia, possibly by neutralizing the immunosuppressive effects of uncontrolled tumor growth. These observations may be useful for the design of immunotherapy trials in metastatic colorectal cancer.