Lack of dendritic cell mobilization into the peripheral blood of cancer patients following standard- or high-dose chemotherapy plus granulocyte-colony stimulating factor.
BACKGROUND
Dendritic cells (DC), the most specialized antigen-presenting cells, can be detected in the peripheral blood (PB) and divided into two subsets of populations, DC1 and DC2, endowed with different functions. The aim of this study was to evaluate the effect on DC release and on their subsets of three regimens utilized to mobilize CD34+ cells into the PB in cancer patients and in normal CD34+ cell donors.


METHODS
The mobilizing sequences were: standard-dose epirubicin+taxol+granulocyte-colony-stimulating factor (G-CSF; 15 patients with advanced breast cancer), high-dose cyclophosphamide (CTX)+G-CSF (10 patients with breast cancer patients and 7 with non-Hodgkin's lymphoma, NHL), and G-CSF alone (5 normal donors of CD34+ cells for allogeneic transplantation). Comparative data were obtained from the steady-state PB of 20 healthy volunteers. For flow cytometric analysis, DC were gated as negative for specific lineage markers (CD3, CD11b, CD14, CD16, CD56, CD19, CD20, CD34) and positive for HLA-DR. The DC1 and DC2 subsets were defined as CD11c and CDw123 positive, respectively.


RESULTS
The percentages of DC at baseline and the time of CD34+ cell peak were: 0.48 and 0.51 for standard-dose chemotherapy (CT); 0.55 and 0.63 for breast cancer after high-dose CTX+G-CSF; 0.53 and 0.71 for NHL after high-dose CTX+G-CSF; and 0.51 and 0.54 for normal donors of CD34+ cells after G-CSF alone (all p=n.s.). Mean DC1/DC2 ratios in each study group at the time of CD34+ cell peak were 0.10, 0.12, and 0.18, respectively. Finally, in the group of healthy volunteers, the percentage of circulating DC was 0.95 and the mean DC1/DC2 ratio was 1.28.


CONCLUSIONS
To our knowledge, this is the first report that demonstrates that both standard-dose or high-dose CT, when utilized together with G-CSF, do not induce DC mobilization into the PB, whereas a reversed DC1/DC2 ratio is observed. Furthermore, a lack of significant DC mobilization after G-CSF alone was also seen, in contrast to what was previously observed by others. These data should be taken in account when evaluating clinical correlations between DC number and CPC engraftment in both the transplantation setting, when monitoring the effects on the immune system of combinations of new drugs and/or cytokines, and when high numbers of DC are required for both experimental and clinical applications.
Ferrari
Silvia
S
Flow Cytometry and Cell Therapy Unit, IRCCS San Matteo University Hospital, 27100 Pavia, Italy.
Rovati
Bianca
B
Porta
Camillo
C
Alessandrino
Paolo Emilio
PE
Bertolini
Alessandro
A
Collovà
Elena
E
Riccardi
Alberto
A
Danova
Marco
M
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D018952:Antigens, CD34 / Q000096:biosynthesis; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000628:therapy; D019070:Cell Lineage; D003131:Combined Modality Therapy / Q000379:methods; D003520:Cyclophosphamide / Q000627:therapeutic use; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000628:therapy*; D017239:Paclitaxel / Q000627:therapeutic use; D018418:Th2 Cells / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D015251:Epirubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D017239:Paclitaxel