Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery.
Dendritic cells (DC) can serve to immunize the newborn immune system to foreign antigen. In a lymphopenic environment, naive T cells undergoing homeostasis-driven proliferation can acquire increased sensitivity to antigen stimulation. Here, we evaluated the capacity of DC to effectively prime the host immune system to elicit antitumor effects in the setting of early lymphoid reconstitution after bone marrow transplantation (BMT). Indeed, bone marrow-derived, cytokine-driven DC pulsed with whole tumor lysates (TP-DC) could, early on, prime a specific and long-lasting antitumor immune response, which mediated the rejection of a lethal challenge of a weakly immunogenic breast tumor. In the therapeutic setting, TP-DC could also inhibit the growth of preexisting breast tumor metastases by repetitive immunizations initiated early after BMT. Spleen T cells obtained from mice immunized with TP-DC early after BMT showed a substantial increase in tumor-specific IFN-gamma production. Our findings demonstrate that it is possible to promote effective antitumor immunity in a defined lymphopenic environment through DC-based immunization.
Asavaroengchai
W
W
Department of Pathology, University of Michigan Medical Center, 1520 MSRB-I, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0666, USA.
Kotera
Y
Y
Mulé
J J
JJ
D000818:Animals; D016026:Bone Marrow Transplantation; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D007371:Interferon-gamma