Cross-presentation of tumor antigens by bone marrow-derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression.
Tumor antigen-specific T-cell tolerance may limit the efficacy of therapeutic cancer vaccines. Direct presentation of antigens by tumor cells incapable of providing adequate costimulation to tumor-specific T cells has been suggested as the basis for this unresponsiveness. Using parent-into-F1 bone marrow (BM) chimeras, this study unambiguously demonstrates that the induction of this tolerant state requires T-cell recognition of tumor antigen presented by BM-derived antigen-presenting cells (APCs), not tumor cells themselves. In the absence of host APC presentation, tumor-specific T cells remained functional, even in the setting of antigen expressed by B-cell lymphomas residing in secondary lymphoid tissues. The intrinsic APC capacity of tumor cells has therefore little influence over T-cell priming versus tolerance, a decision that is regulated at the level of host APCs. (Blood. 2001;98:1070-1077)
Sotomayor
E M
EM
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Borrello
I
I
Rattis
F M
FM
Cuenca
A G
AG
Abrams
J
J
Staveley-O'Carroll
K
K
Levitsky
H I
HI
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002999:Clone Cells / Q000276:immunology; D018450:Disease Progression; D006389:Hemagglutinins, Viral / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D008954:Models, Biological; D009368:Neoplasm Transplantation; D018183:Transplantation Chimera; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000637:transplantation
D000951:Antigens, Neoplasm; D006389:Hemagglutinins, Viral