[Effects of soluble secreted by acute myeloid leukemia cells on differentiation, maturation, apoptosis, and functions of dendritic cells].
OBJECTIVE
Dendritic cells (DCs) play an important role in the immunosurveillance against cancer. It has been shown that the function of DCs is impaired and their population decreases in cancer-bearing hosts. Recent observations suggest that the inability of DCs could be a result of the immunosuppression mediated by soluble factors secreted by tumor cells. This study was to investigate the effects of soluble factors secreted by acute myeloid leukemia (AML) cells on the differentiation, maturation, apoptosis, and functions of DCs derived from normal mononuclear cells.


METHODS
Mononuclear cells were cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF), in the presence or absence of 24-hour culture supernatants from fresh primary AML cells, to generate immature DCs. The maturation of DCs was induced by cytokines IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and prostaglandin-2 (PGE-2). The phenotypic and apoptotic alterations of DCs were evaluated using flow cytometry. Precursor frequency (PF) was calculated to monitor the allostimulatory effects of DCs on CD4+ and CD8+ T cells.


RESULTS
AML cell supernatant-treated DCs showed significantly lower expression of co-stimulatory molecules CD80 and CD86, and reduced response to cytokines IL-1beta, IL-6, TNF-alpha, and PGE-2. The apoptosis rate was significantly lower in AML cell supernatant-treated DCs than in control DCs [(29.4+/-9.5)% vs. (15.1+/-4.2)%, P<0.01]. The allostimulatory effects of AML cell supernatant-treated DCs on CD4+ and CD8+ T cells were significantly lower than those of normal mature DCs [PF: (1.8+/-0.5)% vs. (5.2+/-1.6)% for CD4+ T cells, (2.1+/-0.6)% vs. (6.5+/-2.0)% for CD8+ T cells, P<0.01].


CONCLUSIONS
Soluble factors derived from AML cells could inhibit development and functions of DCs.
Wang
Xing-Bing
XB
Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, PR China.
Liu
Jun
J
Wu
Jing-Sheng
JS
Sun
Zi-Min
ZM
Huang
Shi-Ang
SA
D017209:Apoptosis; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D003470:Culture Media; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D003470:Culture Media; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor