Characterization of dendritic-like cells derived from t(9;22) acute lymphoblastic leukemia blasts.
We asked herein whether functional dendritic-like cells could be generated from t(9;22) acute lymphoblastic leukemia (ALL) blasts. We first determined that the combination of interleukin (IL)-1beta, IL-3, IL-7, tumor necrosis factor-alpha, stem cell factor and CD40 ligand was optimal for generating dendritic-like cells from t(9;22) ALL cell lines. Following 6 days in culture, four of five cell lines demonstrated dendrite-like morphology, upregulation of CCR7, CD54, CD80 and CD86, uptake of extracellular proteins and activation of T cells, and similar results were obtained with blasts from three t(9;22) ALL patients. The dendritic-like cells appeared to be composed of populations resembling both immature and mature dendritic cells (DCs), distinguished by CD80 expression. CD80-CD86+ cells were classified as immature DCs, demonstrating high endocytic capability and inducing minimal allogeneic T cell proliferation, while CD80+CD86+ cells were classified as mature DCs, exhibiting negligible endocytic capability and inducing robust allogeneic T cell proliferation. These mature dendritic-like cells induced autologous cytotoxic T cell responses against the unmodified blasts in a patient who achieved prolonged remission. In summary, CD80+CD86+ cells generated from t(9;22) ALL blasts may be useful in adoptive immunotherapy for t(9;22) ALL.
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Jaewoo
J
Lee
Sheila N
SN
Sait
Meir
M
Wetzler
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen; D015153:Blotting, Western; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D016207:Cytokines / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D014178:Translocation, Genetic
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D008562:Membrane Glycoproteins