Publications Repository

Publications Repository

View Item 
  •   Home
  • ICR Divisions
  • Other ICR Research
  • View Item
  • Home
  • ICR Divisions
  • Other ICR Research
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation

Thumbnail
Publication Date
2008-03
ICR Author
Rhiannon-Taylor, Jessica
Author
Lo, ASY
Taylor, JR
Farzaneh, F
Kemeny, DM
Dibb, NJ
Maher, J
Type
Journal Article
Metadata
Show full item record
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 fins 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)-gamma 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-fins 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. (c) 2007 Elsevier Ltd. All rights reserved.
URL
https://repository.icr.ac.uk/handle/internal/2450
Collections
  • Other ICR Research
Version of record
10.1016/j.molimm.2007.09.010
Language
English
License start date
2008-03
Citation
MOLECULAR IMMUNOLOGY, 2008, 45 pp. 1276 - 1287
Publisher
PERGAMON-ELSEVIER SCIENCE LTD

Browse

All of ICR repositoryICR DivisionsIssue dateAuthorsTitlesSubjectsThis collectionIssue dateAuthorsTitlesSubjects

Statistics

Most popular itemsStatistics by countryMost popular authors
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.