期刊
BLOOD
卷 105, 期 3, 页码 1135-1143出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2004-01-0027
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资金
- NCI NIH HHS [CA79656, CA100850, CA87583] Funding Source: Medline
Tumor antigen-specific T-cell tolerance imposes a significant barrier to the development of effective therapeutic cancer vaccines. Bone marrow-derived antigen-presenting cells (APCs) are critical in the induction of this unresponsive state. Here we show that in vitro treatment of APCs with the tyrosine kinase inhibitor, imatinib mesylate (STI-571), enhances the activation of naive antigen-specific T cells and restores the responsiveness of tolerant T cells from tumor-bearing hosts. Furthermore, in vivo treatment with STI-571 not only prevented the induction of tolerance in tumor-specific CD4(+) T cells, preserving their responsiveness to a subsequent immunization, but also resulted in enhanced vaccine efficacy. These findings demonstrate that tolerance to tumor antigens is not an insurmountable obstacle and points to modulation of AIPC function as a promising strategy in the immunotherapy of cancer. (C) 2005 by The American Society of Hematology.
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