Modulation of antitumour immune responses by intratumoural Stat1 expression

Messina, Nicole L., Banks, Kellie M., Vidacs, Eva, Martin, Ben P., Long, Fennella, Christiansen, Ailsa J., Smyth, Mark J., Clarke, Christopher J. P. and Johnstone, Ricky W. (2013) Modulation of antitumour immune responses by intratumoural Stat1 expression. Immunology and Cell Biology, 91 9: 556-567. doi:10.1038/icb.2013.41


Author Messina, Nicole L.
Banks, Kellie M.
Vidacs, Eva
Martin, Ben P.
Long, Fennella
Christiansen, Ailsa J.
Smyth, Mark J.
Clarke, Christopher J. P.
Johnstone, Ricky W.
Title Modulation of antitumour immune responses by intratumoural Stat1 expression
Formatted title
Modulation of antitumour immune responses by intratumoural Stat1 expression
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
1440-1711
Publication date 2013-10
Year available 2013
Sub-type Article (original research)
DOI 10.1038/icb.2013.41
Open Access Status
Volume 91
Issue 9
Start page 556
End page 567
Total pages 12
Place of publication London, United Kingdom
Publisher Nature
Collection year 2014
Language eng
Formatted abstract
Signal transducer and activator of transcription 1 (Stat1) mediates anti-viral responses and cytokine-driven anti-proliferative, apoptotic and immunomodulatory activities. As de-regulated Stat1 function can affect tumour progression we sought to elucidate the effects of tumour cell-intrinsic Stat1 expression on immunosurveillance. Knockout of Stat1 enhanced the development of sarcomas induced by the chemical carcinogen 3-methylcholanthrene (MCA). Growth of transplanted MCA-induced Stat1−/− sarcomas was suppressed in wild-type mice compared to growth in Stat1−/− and immunocompromised recipients. Co-depletion of NK and CD8+ T cells from wild-type mice facilitated Stat1-deficient tumour growth whereas depletion of CD4+ T cells and CD8+ T cells did not. In vitro and in vivo analysis of the tumours implicated a role for NK cell-mediated, perforin-dependent killing of Stat1-deficient tumours. Interestingly, restoration of Stat1 expression in Stat1−/− tumours resulted in diminished involvement of NK cells and increased contribution of CD8+ T cells in anti-tumour responses. Therefore, Stat1 expression within tumour cells modulated anti-tumour immune responses by altering the dominant immune effector cell involvement from NK cells to CD8+ T cells in the absence or presence of Stat1 respectively.
Keyword NK cells
Signal transduction
Stat1
Transcription factors
Tumour immunity
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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