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, Emmanuel Katsanis

Research output: Contribution to journalArticle

17 Scopus citations

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-κB, 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.

Original languageEnglish (US)
Pages (from-to)1049-1059
Number of pages11
JournalJournal of Leukocyte Biology
Volume83
Issue number4
DOIs
StatePublished - Apr 1 2008

Keywords

  • CD4CD25 regulatory T lymphocytes
  • Chaperone-rich cell lysate
  • Dendritic cells
  • Monocytes-macrophages

ASJC Scopus subject areas

  • Cell Biology

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    Larmonier, N., Cantrell, J., LaCasse, C., Li, G., Janikashvili, N., Situ, E., Sepassi, M., Andreansky, S., & Katsanis, E. (2008). Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression. Journal of Leukocyte Biology, 83(4), 1049-1059. https://doi.org/10.1189/jlb.0907635