Augmentation of antitumor immune responses after adoptive transfer of bone marrow derived from donors immunized with tumor lysate-pulsed dendritic cells.
We demonstrated previously that tumor lysate-pulsed dendritic cells (TP-DC) could mediate a specific and long-lasting antitumor immune response against a weakly immunogenic breast tumor during early lymphoid reconstitution. The purpose of this study was to examine the potential therapeutic efficacy of bone marrow transplants from TP-DC-vaccinated donors. In 2 aggressive metastatic models, bone marrow transplantation with donor bone marrow cells from TP-DC-immunized mice mediated a tumor-specific immune response in the recipient, and this caused regressions of preexisting tumor metastases. After vaccination with TP-DC, donors harbored increased numbers of both activated CD4+ and CD8+ T-cell populations in the bone marrow. Adoptive transfer of T cells purified from the bone marrow of TP-DC-vaccinated mice led to a reduction in preestablished lung metastases, whereas depletion of T cells from bone marrow abolished this effect. By using T cells derived from the bone marrow of TP-DC-vaccinated major histocompatibility complex class I and class II knockout mice, the effector cells required for the observed antitumor effect were determined to be major histocompatibility complex class I-restricted CD8+ T cells. Additionally, the tumor burden in TP-DC-immunized transplant recipients could be reduced further by repetitive TP-DC immunizations after bone marrow transplantation. Collectively, these results demonstrate an important therapeutic role of bone marrow from TP-DC-immunized donors and raise the potential for this approach in patients with advanced cancer.
Asavaroengchai
W
W
Department of Surgery and Tumor Immunology and Immunotherapy Program of the Comprehensive Cancer Center and Graduate Program in Immunology, University of Michigan Health System, Ann Arbor, Michigan, USA.
Kotera
Y
Y
Koike
N
N
Pilon-Thomas
S
S
Mulé
J J
JJ
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D007371:Interferon-gamma