Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0907635 on January 3, 2008

Published online before print January 3, 2008
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(Journal of Leukocyte Biology. 2008;83:1049-1059.)
© 2008 by Society for Leukocyte Biology

Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression

Nicolas Larmonier, Jessica Cantrell, Collin LaCasse, Gang Li, Nona Janikashvili, Elaine Situ, Marjan Sepassi, Samita Andreansky and Emmanuel Katsanis1

Department of Pediatrics, Steele Children’s Research Center, University of Arizona, Tucson, Arizona, USA

1 Correspondence: University of Arizona, Department of Pediatrics, 1501 N. Campbell Ave., P.O. Box 245073, Tucson, AZ 85724-5073, USA. E-mail: katsanis{at}peds.arizona.edu

ABSTRACT

CD4+CD25+ regulatory T lymphocytes (Tregs) critically contribute to the mechanisms of cancer-induced tolerance. These cells suppress anti-tumoral CD8+ and CD4+ T lymphocytes and can also restrain the function of APCs. We have previously documented the immunostimulatory effects of a chaperone-rich cell lysate (CRCL) anti-cancer vaccine. Tumor-derived CRCL induces tumor immunity in vivo, partly by promoting dendritic cell (DC) and macrophage activation. In the current study, we evaluated the effects of CD4+CD25+forkhead box P3+ Tregs isolated from mice bearing 12B1 bcr-abl+ leukemia on DC and macrophages that had been activated by 12B1-derived CRCL. CRCL-activated DC and macrophages resisted Treg suppression, as the production of proinflammatory cytokines, the activation of transcription factor NF-{kappa}B, and their immunostimulatory potential was unaffected by Tregs. Our results thus highlight CRCL as a powerful adjuvant endowed with the capacity to overcome tumor-induced Treg-inhibitory effects on APCs.

Key Words: dendritic cells • monocytes-macrophages • CD4+CD25+ regulatory T lymphocytes • chaperone-rich cell lysate




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N. Larmonier, N. Janikashvili, C. J. LaCasse, C. B. Larmonier, J. Cantrell, E. Situ, T. Lundeen, B. Bonnotte, and E. Katsanis
Imatinib Mesylate Inhibits CD4+CD25+ Regulatory T Cell Activity and Enhances Active Immunotherapy against BCR-ABL- Tumors
J. Immunol., November 15, 2008; 181(10): 6955 - 6963.
[Abstract] [Full Text] [PDF]


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