Hyperthermia enhances CTL cross-priming

Hongzhen Shi, Tinghua Cao, John E. Connolly, Laurence Monnet, Lynda Bennett, Sylvie Chapel, Claude Bagnis, Patrice Mannoni, Jean Davoust, A. Karolina Palucka, Jacques Banchereau

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Dendritic cells (DCs) loaded with killed allogeneic melanoma cells can cross-prime naive CD8+ T cells to differentiate into melanoma-specific CTLs in 3-wk cultures. In this study we show that DCs loaded with killed melanoma cells that were heated to 42°C before killing are more efficient in cross-priming of naive CD8+ T cells than DCs loaded with unheated killed melanoma cells. The enhanced cross-priming was demonstrated by several parameters: 1) induction of naive CD8+ T cell differentiation in 2-wk cultures, 2) enhanced killing of melanoma peptide-pulsed T2 cells, 3) enhanced killing of HLA-A*0201+ melanoma cells in a standard 4-h chromium release assay, and 4) enhanced capacity to prevent tumor growth in vitro in a tumor regression assay. Two mechanisms might explain the hyperthermia-induced enhanced cross-priming. First, heat-treated melanoma cells expressed increased levels of 70-kDa heat shock protein (HSP70), and enhanced cross-priming could be reproduced by overexpression of HSP70 in melanoma cells transduced with HSP70 encoding lentiviral vector. Second, hyperthermia resulted in the increased transcription of several tumor Ag-associated Ags, including MAGE-B3, -B4, -A8, and -A10. Thus, heat treatment of tumor cells permits enhanced cross-priming, possibly via up-regulation of both HSPs and tumor Ag expression.

Original languageEnglish (US)
Pages (from-to)2134-2141
Number of pages8
JournalJournal of Immunology
Volume176
Issue number4
DOIs
StatePublished - Feb 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Shi, H., Cao, T., Connolly, J. E., Monnet, L., Bennett, L., Chapel, S., Bagnis, C., Mannoni, P., Davoust, J., Palucka, A. K., & Banchereau, J. (2006). Hyperthermia enhances CTL cross-priming. Journal of Immunology, 176(4), 2134-2141. https://doi.org/10.4049/jimmunol.176.4.2134