Please use this identifier to cite or link to this item:
|Title:||Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation|
|Citation:||Lo, A.S.Y., Taylor, J.R., Farzaneh, F., Kemeny, D.M., Dibb, N.J., Maher, J. (2008). Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation. Molecular Immunology 45 (5) : 1276-1287. ScholarBank@NUS Repository.|
|Abstract:||Aberrant growth factor production is a prevalent mechanism in tumourigenesis. If T-cells responded positively to a cancer-derived cytokine, this might result in selective enhancement of function within the tumour microenvironment. Here, we have chosen colony-stimulating factor-1 (CSF-1) as a candidate to test this concept. CSF-1 is greatly overproduced in many cancers but has no direct effects upon T-lymphocytes, which do not express the c-fms-encoded CSF-1 receptor. To confer CSF-1-responsiveness, we have expressed the human c-fms gene in immortalized and primary T-cells. Addition of soluble CSF-1 resulted in synergistic enhancement of IL-2-driven T-cell proliferation. CSF-1 also co-stimulated the production of interferon (IFN)-γ by activated T-cells. These effects required Y809 of the CSF-1R and activation of the Ras-MEK-MAP kinase cascade, but were independent of PI3K signalling. T-cells that express c-fms are also responsive to membrane-anchored CSF-1 (mCSF-1) which, unlike its soluble counterpart, could co-stimulate IL-2 production. CSF-1 promoted chemotaxis of c-fms-expressing primary human T-cells and greatly augmented proliferation mediated by a tumour-targeted chimeric antigen receptor, with preservation of tumour cytolytic activity. Taken together, these data establish that T-cells may be genetically modified to acquire responsiveness to CSF-1 and provide proof-of-principle for a novel strategy to enhance the effectiveness of adoptive T-cell immunotherapy. © 2007 Elsevier Ltd. All rights reserved.|
|Source Title:||Molecular Immunology|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Mar 19, 2018
WEB OF SCIENCETM
checked on Dec 31, 2018
checked on Nov 10, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.