Signaling pathways induced by a tumor-derived vaccine in antigen presenting cells

Jessica Cantrell, Claire Larmonier, Nona Janikashvili, Sara Bustamante, Jennifer Fraszczak, Amanda Herrell, Tamara Lundeen, Collin J LaCasse, Elaine Situ, Nicolas Larmonier, Emmanuel Katsanis

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

We have previously reported on the anti-tumoral potential of a chaperone-rich cell lysate (CRCL) vaccine. Immunization with CRCL generated from tumors elicits specific T and NK cell-dependent immune responses leading to protective immunity in numerous mouse tumor models. CRCL provides both a source of tumor antigens and danger signals leading to dendritic cell activation. In humans, tumor-derived CRCL induces dendritic cell activation and CRCL-loaded dendritic cells promote the generation of cytotoxic T lymphocytes in vitro. The current study was designed to identify the signaling events and modifications triggered by CRCL in antigen presenting cells. Our results indicate that tumor-derived CRCL not only promotes the activation of dendritic cells, but also significantly fosters the function of macrophages that thus appear as major targets of this vaccine. Activation of both cell types is associated with the induction of the MAP kinase pathway, the phosphorylation of STAT1, STAT5 and AKT and with transcription factor NF-κB activation in vitro and in vivo. These results thus provide important insights into the mechanisms by which CRCL-based vaccines exert their adjuvant effects on antigen presenting cells.

Original languageEnglish (US)
Pages (from-to)535-544
Number of pages10
JournalImmunobiology
Volume215
Issue number7
DOIs
StatePublished - Jul 1 2010

Keywords

  • Cell signaling
  • Dendritic cells
  • Macrophages
  • Tumor vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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  • Cite this

    Cantrell, J., Larmonier, C., Janikashvili, N., Bustamante, S., Fraszczak, J., Herrell, A., Lundeen, T., J LaCasse, C., Situ, E., Larmonier, N., & Katsanis, E. (2010). Signaling pathways induced by a tumor-derived vaccine in antigen presenting cells. Immunobiology, 215(7), 535-544. https://doi.org/10.1016/j.imbio.2009.09.006