Imatinib mesylate (STI-571) enhances antigen-presenting cell function and overcomes tumor-induced CD4 + T-cell tolerance

Hongwei Wang, Fengdong Cheng, Alex Cuenca, Pedro Horna, Zheng Zheng, Kapil Bhalla, Eduardo M. Sotomayor

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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 APC function as a promising strategy in the immunotherapy of cancer.

Original languageEnglish (US)
Pages (from-to)1135-1143
Number of pages9
JournalBlood
Volume105
Issue number3
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

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T-cells
Antigen-Presenting Cells
Tumors
T-Lymphocytes
Neoplasm Antigens
Neoplasms
Bearings (structural)
Immunization
Cancer Vaccines
Protein-Tyrosine Kinases
Immunotherapy
Bone
Therapeutics
Vaccines
Bone Marrow
Chemical activation
Modulation
Antigens
Imatinib Mesylate

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Imatinib mesylate (STI-571) enhances antigen-presenting cell function and overcomes tumor-induced CD4 + T-cell tolerance . / Wang, Hongwei; Cheng, Fengdong; Cuenca, Alex; Horna, Pedro; Zheng, Zheng; Bhalla, Kapil; Sotomayor, Eduardo M.

In: Blood, Vol. 105, No. 3, 01.02.2005, p. 1135-1143.

Research output: Contribution to journalArticle

Wang, Hongwei ; Cheng, Fengdong ; Cuenca, Alex ; Horna, Pedro ; Zheng, Zheng ; Bhalla, Kapil ; Sotomayor, Eduardo M. / Imatinib mesylate (STI-571) enhances antigen-presenting cell function and overcomes tumor-induced CD4 + T-cell tolerance In: Blood. 2005 ; Vol. 105, No. 3. pp. 1135-1143.
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