CD11c+ blood dendritic cells induce antigen-specific cytotoxic T lymphocytes with similar efficiency compared to monocyte-derived dendritic cells despite higher levels of MHC class I expression.
Dendritic cell (DC) immunotherapy for cancer has shown promising results in phase I and II clinical trials. Most studies have used monocyte-derived DCs (MoDCs) but their poor migratory capacity in vivo has emerged as a key issue. The natural circulating peripheral blood CD11c+ DC precursors (BDCs) may be an attractive alternative to MoDCs, as they can be isolated rapidly in sufficient quantities, and have superior migratory and T helper-1-inducing capacity in vitro. We performed the first comparative analysis of the ability of autologous BDCs and MoDCs in healthy donors to induce tumor-specific cytotoxic T lymphocytes (CTLs). BDCs expressed significantly higher levels of major histocompatibility complex class I and CD83 in the absence of exogenous stimuli compared with MoDCs. After activation with polyinosinic-polycytidylic acid, BDCs expressed higher levels of major histocompatibility complex class I, CD40, CD80, and CD83, and secreted higher levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-8 compared with MoDCs. Despite these differences, both preparations secreted similar levels of IL-12 in response to polyinosinic-polycytidylic acid and, importantly, induced CTL responses of similar magnitude and affinity against influenza matrix protein and MART-1. The ability of BDCs to induce efficient CTL responses, combined with their migratory capacity, makes them an appealing alternative to be investigated in clinical immunotherapy research protocols.
Radford
Kristen J
KJ
Mater Medical Research Institute, South Brisbane, Queensland, Australia.
Turtle
Cameron J
CJ
Kassianos
Andrew J
AJ
Hart
Derek N J
DN
D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D039521:CD11c Antigen / Q000097:blood / Q000276:immunology*; D023201:CD40 Ligand / Q000494:pharmacology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D058965:MART-1 Antigen; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D039521:CD11c Antigen; C119956:CMRF-56 antigen; D016207:Cytokines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D014763:Viral Matrix Proteins; C448634:influenza matrix peptide (58-66); D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma; D011070:Poly I-C