Please use this identifier to cite or link to this item:
https://scholarbank.nus.edu.sg/handle/10635/24730
DC Field | Value | |
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dc.title | Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation | |
dc.contributor.author | Lo, A.S.Y. | |
dc.contributor.author | Taylor, J.R. | |
dc.contributor.author | Farzaneh, F. | |
dc.contributor.author | Kemeny, D.M. | |
dc.contributor.author | Dibb, N.J. | |
dc.contributor.author | Maher, J. | |
dc.date.accessioned | 2011-07-26T06:53:46Z | |
dc.date.available | 2011-07-26T06:53:46Z | |
dc.date.issued | 2008 | |
dc.identifier.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. | |
dc.identifier.issn | 01615890 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/24730 | |
dc.description.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. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.molimm.2007.09.010 | |
dc.source | Scopus | |
dc.subject | Adoptive immunotherapy | |
dc.subject | c-fms | |
dc.subject | CSF-1 | |
dc.subject | T-cell | |
dc.type | Article | |
dc.contributor.department | MICROBIOLOGY | |
dc.description.sourcetitle | Molecular Immunology | |
dc.description.volume | 45 | |
dc.description.issue | 5 | |
dc.description.page | 1276-1287 | |
dc.identifier.isiut | 000253030000009 | |
Appears in Collections: | Staff Publications |
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