Macrophages orchestrate the immune response to tumor cell death

Michael J. Gough, Alan A. Melcher, Marka R. Crittenden, David S. Riddle, Emmanouela Linardakis, Anja N. Ruchatz, Lisa M. Emiliusen, Richard G. Vile, Atique Ahmed

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

The mechanisms by which the immune system distinguishes normal developmental cell death from pathological immunogenic cell killing are central to effective cancer immunotherapy. Using HSVtk suicide gene therapy, we showed that macrophages can distinguish between tumor cells dying through classical apoptosis and tumor cells engineered to die through nonapoptotic mechanisms, resulting in secretion of either immunosuppressive cytokines (interleukin 10 and transforming growth factor β) or inflammatory cytokines (tumor necrosis factor α or interleukin 1β), respectively. Additionally heat shock protein 70 acts as one component of a bimodal alarm signal that activates macrophages in the presence of stressful, immunogenic tumor cell killing. These differential responses of macrophages can also be used to vaccinate mice against tumor challenge, using adoptive transfer, as well as to cure mice of established tumors.

Original languageEnglish (US)
Pages (from-to)7240-7247
Number of pages8
JournalCancer research
Volume61
Issue number19
StatePublished - Oct 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gough, M. J., Melcher, A. A., Crittenden, M. R., Riddle, D. S., Linardakis, E., Ruchatz, A. N., Emiliusen, L. M., Vile, R. G., & Ahmed, A. (2001). Macrophages orchestrate the immune response to tumor cell death. Cancer research, 61(19), 7240-7247.