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 therapeut ic cancer vaccines. Direct presentation of antigens by tumor cells incapabl e of providing adequate costimulation to tumor-specific T cells has been su ggested as the basis for this unresponsiveness. Using parent-into-F1 bone m arrow (BM) chimeras, this study unambiguously demonstrates that the inducti on of this tolerant state requires T-cell recognition of tumor antigen pres ented by BM-derived antigen-presenting cells (APCs), not tumor cells themse lves. In the absence of host APC presentation, tumor-specific T cells remai ned functional, even in the setting of antigen expressed by B-cell lymphoma s residing in secondary lymphoid tissues. The intrinsic APC capacity of tum or cells has therefore little influence over T-cell priming versus toleranc e, a decision that is regulated at the level of host APCs. (C) 2001 by The American Society of Hematology.