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Modulation of antitumour immune responses by intratumoural Stat1 expression.
- Source :
- Immunology & Cell Biology; Oct2013, Vol. 91 Issue 9, p556-567, 12p
- Publication Year :
- 2013
-
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<superscript>−/−</superscript> sarcomas was suppressed in wild-type mice compared to growth in Stat1<superscript>−/−</superscript> and immunocompromised recipients. Co-depletion of NK and CD8<superscript>+</superscript> T cells from wild-type mice facilitated Stat1-deficient tumour growth whereas depletion of CD4<superscript>+</superscript> T cells and CD8<superscript>+</superscript> 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<superscript>−/−</superscript> tumours resulted in diminished involvement of NK cells and increased contribution of CD8<superscript>+</superscript> 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<superscript>+</superscript> T cells in the absence or presence of Stat1 respectively. [ABSTRACT FROM AUTHOR]
- Subjects :
- IMMUNE response
T cells
CANCER cells
CELLULAR immunity
CYTOKINES
Subjects
Details
- Language :
- English
- ISSN :
- 08189641
- Volume :
- 91
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Immunology & Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 90606870
- Full Text :
- https://doi.org/10.1038/icb.2013.41