Cyclophosphamide induces bone marrow to yield higher numbers of precursor dendritic cells in vitro capable of functional antigen presentation to T cells in vivo.
We have shown recently that cyclophosphamide (CTX) treatment induced a marked increase in the numbers of immature dendritic cells (DCs) in blood, coinciding with enhanced antigen-specific responses of the adoptively transferred CD8(+) T cells. Because this DC expansion was preceded by DC proliferation in bone marrow (BM), we tested whether BM post CTX treatment can generate higher numbers of functional DCs. BM was harvested three days after treatment of C57BL/6 mice with PBS or CTX and cultured with GM-CSF/IL-4 in vitro. Compared with control, BM from CTX-treated mice showed faster generation and yielded higher numbers of DCs with superior activation in response to toll-like receptor (TLR) agonists. Vaccination with peptide-pulsed DCs generated from BM from CTX-treated mice induced comparable adjuvant effects to those induced by control DCs. Taken together, post CTX BM harbors higher numbers of DC precursors capable of differentiating into functional DCs, which be targeted to create host microenvironment riches in activated DCs upon treatment with TLR agonists.
Salem
Mohamed L
ML
Surgery Department and Hollings Cancer Center, Medical University of South Carolina, Charleston, 29425, USA. salemm@musc.edu
El-Naggar
Sabry A
SA
Cole
David J
DJ
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018845:CD11 Antigens / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology; D019172:Transplantation Conditioning
D018906:Antineoplastic Agents, Alkylating; D018845:CD11 Antigens; D011948:Receptors, Antigen, T-Cell; D051193:Toll-Like Receptors; D003520:Cyclophosphamide