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


METHODS
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.
Melichar
Bohuslav
B
Departments of Oncology & Radiotherapy, Charles University Medical School & Teaching Hospital, 23, 500 05 Hradec Králové, Czech Republic. melichar@fnhk.cz
Touskova
Miroslava
M
Vesely
Pavel
P
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D016130:Immunophenotyping; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged
D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin