Macrophages orchestrate the immune response to tumor cell death

M. J. Gough, A. A. Melcher, A. Ahmed, M. R. Crittenden, D. S. Riddle, E. Linardakis, A. N. Ruchatz, Richard Geoffrey Vile, R. G. Vile

Research output: Contribution to journalArticle

75 Citations (Scopus)

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

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Cell Death
Macrophages
Neoplasms
Cytokines
HSP70 Heat-Shock Proteins
Adoptive Transfer
Transforming Growth Factors
Immunosuppressive Agents
Interleukin-1
Genetic Therapy
Interleukin-10
Immunotherapy
Suicide
Immune System
Tumor Necrosis Factor-alpha
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

Macrophages orchestrate the immune response to tumor cell death. / Gough, M. J.; Melcher, A. A.; Ahmed, A.; Crittenden, M. R.; Riddle, D. S.; Linardakis, E.; Ruchatz, A. N.; Vile, Richard Geoffrey; Vile, R. G.

In: Cancer Research, Vol. 61, No. 19, 01.10.2001, p. 7240-7247.

Research output: Contribution to journalArticle

Gough, MJ, Melcher, AA, Ahmed, A, Crittenden, MR, Riddle, DS, Linardakis, E, Ruchatz, AN, Vile, RG & Vile, RG 2001, 'Macrophages orchestrate the immune response to tumor cell death', Cancer Research, vol. 61, no. 19, pp. 7240-7247.
Gough MJ, Melcher AA, Ahmed A, Crittenden MR, Riddle DS, Linardakis E et al. Macrophages orchestrate the immune response to tumor cell death. Cancer Research. 2001 Oct 1;61(19):7240-7247.
Gough, M. J. ; Melcher, A. A. ; Ahmed, A. ; Crittenden, M. R. ; Riddle, D. S. ; Linardakis, E. ; Ruchatz, A. N. ; Vile, Richard Geoffrey ; Vile, R. G. / Macrophages orchestrate the immune response to tumor cell death. In: Cancer Research. 2001 ; Vol. 61, No. 19. pp. 7240-7247.
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