Journal
BLOOD
Volume 107, Issue 7, Pages 2871-2878Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-07-3014
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Funding
- NCI NIH HHS [P50CA96888, P01CA15396, CA87583, CA100850] Funding Source: Medline
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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.
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