In vivo disruption of tolerogenic cross-presentation mechanisms uncovers an effective T-cell activation by B-cell lymphomas leading to antitumor immunity.
Bone marrow-derived antigen-presenting cells (APCs) play a central role in the induction of tolerance to tumor antigens expressed by B-cell lymphomas. Here we show that in vivo disruption of this APC-mediated tolerogenic mechanism unveils an intrinsic ability of malignant B cells to efficiently present tumor antigens to antigen-specific CD4+ T cells, resulting in a strong antitumor effect. This intrinsic antigen-presenting ability of malignant B cells is, however, overridden by tolerogenic bone marrow-derived APCs, leading instead to T-cell unresponsiveness and lack of antitumor effect. These results highlight the concept that therapeutic strategies aimed at enhancing the antigen-presenting function of B-cell lymphomas might not succeed unless the tolerogenic mechanisms mediated by bone marrow-derived APCs are disrupted in the first place.
Horna
Pedro
P
Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, MRC 4 East, Rm 4072-H, 12902 Magnolia Dr, Tampa, FL 33612-9497, USA.
Cuenca
Alex
A
Cheng
Fengdong
F
Brayer
Jason
J
Wang
Hong-Wei
HW
Borrello
Ivan
I
Levitsky
Hyam
H
Sotomayor
Eduardo M
EM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines