Malignant counterpart of myeloid dendritic cell (DC) belonging to acute myelogenous leukemia (AML) exhibits a dichotomous immunoregulatory potential.
Dendritic cells (DCs) play a central role in immune regulation. Some leukemic cells are argued to be malignant counterparts of DC because of their ability to differentiate into leukemic DC. We characterize DC-like leukemia homogenously expressing CD11c+CD86+ in acute myelogenous leukemia patients. They express the Wilms' tumor-1 antigen and common DC phenotypes (i.e., fascin+, CD83+, and DR+) directly. Purified leukemic cells produce interleukin-12 (IL-12) simultaneously with Fas ligand (FasL) and IL-6, which may suppress T cell-mediated immunity. These cells can elicit strong allogeneic T cell responses as well as induce tumor-specific CD8+ cytotoxic T cells, suggesting that they effectively present tumor-associated antigens. In contrast, they drive primary T cells toward apoptosis mediated in a tumor-specific way by a Fas-FasL interaction. Taken together, DC-like leukemia uniquely influences immune surveillance in contradictory ways, some of which may be involved in the mechanism of immune escape.
Fujii
Shin-ichiro
S
The Center for Bone Marrow Transplantation and Immunotherapy, Institute for Clinical Research, Kumamoto National Hospital, Japan. fujiis@mail.rockefeller.edu
Shimizu
Kanako
K
Koji
Fujimoto
F
Kawano
Fumio
F
D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D051940:B7-2 Antigen; D039521:CD11c Antigen / Q000032:analysis; D016022:Case-Control Studies; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D025721:WT1 Proteins / Q000032:analysis
D015703:Antigens, CD; D051940:B7-2 Antigen; D039521:CD11c Antigen; C497964:CD86 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D025721:WT1 Proteins; D018664:Interleukin-12