CD64 surface expression on neutrophils and monocytes is significantly up-regulated after stimulation with granulocyte colony-stimulating factor during CHOP chemotherapy for patients with non-Hodgkin's lymphoma.
The present study was performed to examine whether the expression of CD64 Fc gamma receptor type I (FcgammaRI) on both neutrophils and monocytes can be modulated by multiple daily administrations of granulocyte colony-stimulating factor (G-CSF) to patients with non-Hodgkin's lymphoma in neutropenia caused by CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. The expression of CD64 was determined by flow cytometric analysis at the following time points: before chemotherapy, at the nadir of the neutrophil count, at the fifth day after the start of G-CSF administration, and at more than 8 days after the start of G-CSF administration. CD64 expression was enhanced in patients given G-CSF during CHOP treatment, whereas CD64 expression remained unchanged in patients not given G-CSF CD64 expression levels on both neutrophils and monocytes were significantly up-regulated by the daily administration of G-CSF and reached peak levels at day 5 (P = .0007). Thereafter, expression on both cell types remained at almost the same levels as on day 5 for the rest of the treatment course, even though G-CSF therapy continued for 3 to 5 more days. Interestingly, CD64 expression on monocytes was already increased significantly (P = .0001) at the nadir of the neutrophil count relative to the baseline before chemotherapy and then was additionally up-regulated by day 5 after the start of G-CSF injections (P = .019). In antibody-dependent cellular cytotoxicity assays, we found that rituximab-mediated cell lysis was significantly enhanced at day 5 after the start of G-CSF treatment (P = .01). In conclusion, this study shows that multiple doses of G-CSF administered to lymphoma patients with neutropenia due to CHOP chemotherapy can enhance CD64 expression on both neutrophils and monocytes. Peak CD64 levels are reached at day 5 of G-CSF treatment, resulting in an activation of the rituximab-mediated antitumor ability of these effector cells. This finding may be useful in determining the optimal timing of administration for an antibody such as rituximab in a chemotherapeutic strategy designed to exert a maximal effect against tumor cells.
Kakinoki
Yasutaka
Y
Department of Internal Medicine, Asahikawa Kosei Hospital, Asahikawa, Japan. yasukaki@seagreen.ocn.ne.jp
Kubota
Hiroya
H
Yamamoto
Yasushi
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D018951:Antigens, CD20 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics; D000069283:Rituximab; D015854:Up-Regulation / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D017452:Receptors, IgG; D016179:Granulocyte Colony-Stimulating Factor; D000069283:Rituximab; C072115:nartograstim