PMID- 16552959 OWN - NLM STAT- MEDLINE DCOM- 20070713 LR - 20231213 VI - 24 IP - 11 DP - 2005 Nov TI - [In vitro stimulation of specific antileukemia T-cell response by dendritic cells derived from CD14+ acute monocytic leukemia cells]. PG - 1338-44 AB - BACKGROUND & OBJECTIVE: Dendritic cells (DCs) or DC-like cells had been successfully induced in vitro from leukemia cells, which may provide a promising immunotherapeutic protocol for leukemia. This study was designed to investigate the efficiency of in vitro generation of dendritic cells from CD14+ acute myelomonocytic (M4) or monocytic (M5) leukemia cells and their ability of stimulating specific antileukemia T-cell response. METHODS: Bone marrow mononuclear cells (BMMNCs) were isolated from 5 M4/M5 leukemia patients with high CD14 expression, and then divided into 3 groups: adherent leukemia cells, nonadherent blasts, and total unfractioned blasts. CD14 expression of the 3 groups was evaluated by flow cytometry (FCM). When cultured with or without granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) for 7-10 days, monocytic leukemia cell-derived dendritic cells (Mo-LDCs) were identified through morphologic observation and immunophenotype analysis using FCM. The immune function of Mo-LDCs was detected through allogeneic mixed lymphocyte reaction (Allo-MLR) and cytotoxicity assay of antileukemia cytotoxic T lymphocytes (CTLs). The leukemic origin of Mo-LDCs was confirmed by chromosomal karyotype analysis combined with the aberrant expression of myeloid antigens. RESULTS: The amount of CD14+ cells, which could differentiate into CD83+ mature DCs under induction of the cytokine combination, was higher in adherent leukemia cells than in nonadherent blasts and total unfractioned blasts. Regarding each 3 cell groups of the same patient or the unfractioned blasts of various patients, initial CD14 expression was positively related to the yield of CD83+ DCs after induction (r = 0.967, P = 0.007). Mo-LDCs exhibited typical morphology and phenotype as mature DCs, induced potent proliferation of homogeneous T cells in Allo-MLR, stimulated the expansion of leukemia-specific CTLs, and continued to possess the cytogenetic abnormalities of the original leukemia, as well as the aberrant expression of myeloid antigens. CONCLUSIONS: In M4/M5 subtype of AML, CD14+ cells could differentiate into immune-competent Mo-LDCs under the induction of the cytokine combination. CD14 expression level may predict the DCs differentiation ability of monocytic leukemia. Mo-LDCs, which possess the classical phenotype and function of DCs, as well as the abnormal leukemic antigens, may be useful for the immunotherapy of M4/M5 AML. FAU - Sheng, Li-Xia AU - Sheng LX AD - Department of Hematology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu, 213000, PR China. FAU - Xie, Xiao-Bao AU - Xie XB FAU - Qiu, Guo-Qiang AU - Qiu GQ FAU - Gu, Wei-Ying AU - Gu WY FAU - Wang, Zhi-Lin AU - Wang ZL FAU - Wu, Hao-Qing AU - Wu HQ LA - chi PT - Journal Article PL - China TA - Ai Zheng JT - Ai zheng = Aizheng = Chinese journal of cancer JID - 9424852 RN - 0 (Antigens, CD) RN - 0 (Immunoglobulins) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Membrane Glycoproteins) SB - IM MH - Adolescent MH - Aged, 80 and over MH - Antigens, CD/metabolism MH - Cell Differentiation MH - Cells, Cultured MH - Dendritic Cells/*immunology/pathology MH - Female MH - Humans MH - Immunoglobulins/metabolism MH - Leukemia, Monocytic, Acute/immunology/*pathology MH - Lipopolysaccharide Receptors/*analysis MH - Lymphocyte Activation MH - Lymphocyte Culture Test, Mixed MH - Male MH - Membrane Glycoproteins/metabolism MH - Middle Aged MH - T-Lymphocytes, Cytotoxic/*immunology MH - CD83 Antigen EDAT- 2006/03/24 09:00 MHDA- 2007/07/14 09:00 CRDT- 2006/03/24 09:00 PHST- 2006/03/24 09:00 [pubmed] PHST- 2007/07/14 09:00 [medline] PHST- 2006/03/24 09:00 [entrez] PST - ppublish SO - Ai Zheng. 2005 Nov;24(11):1338-44.