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dc.contributor.authorLo, ASY
dc.contributor.authorTaylor, JR
dc.contributor.authorFarzaneh, F
dc.contributor.authorKemeny, DM
dc.contributor.authorDibb, NJ
dc.contributor.authorMaher, J
dc.date.accessioned2018-08-30T13:46:51Z
dc.date.issued2008-03
dc.identifier5
dc.identifier.citationMOLECULAR IMMUNOLOGY, 2008, 45 pp. 1276 - 1287
dc.identifier.issn0161-5890
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2450
dc.identifier.doi10.1016/j.molimm.2007.09.010
dc.description.abstractAberrant 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.
dc.format.extent1276 - 1287
dc.languageeng
dc.language.isoeng
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.titleHarnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation
dc.typeJournal Article
rioxxterms.versionofrecord10.1016/j.molimm.2007.09.010
rioxxterms.licenseref.startdate2008-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMOLECULAR IMMUNOLOGY
pubs.notesaffiliation: Maher, J (Reprint Author), Kings Coll London, Breast Canc Biol Grp, Div Canc Studies, Guys Hosp Campus,St Thomas St, London SE1 9RT, England. Maher, John, Kings Coll London, Breast Canc Biol Grp, Div Canc Studies, London SE1 9RT, England. Lo, Agnes Shuk Yee, Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Taylor, Jessica Rhiannon, Breakthrough Breast Canc Res Ctr, Canc Genet & Epigenet, Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. Farzaneh, Farzin, Kings Coll London, Dept Haematol Med, Rayne Inst, London SE5 9NU, England. Kemeny, David Michael, Natl Univ Singapore, Immunol Programme, Singapore 117597, Singapore. Kemeny, David Michael, Natl Univ Singapore, Dept Microbiol, Singapore 117597, Singapore. Dibb, Nicholas John, Univ London Imperial Coll Sci Technol & Med, IRDB, London W12 0NN, England. keywords: CSF-1; c-fms; T-cell; adoptive immunotherapy keywords-plus: FACTOR-I RECEPTOR; GYNECOLOGIC MALIGNANCIES; SIGNAL-TRANSDUCTION; DENDRITIC CELLS; KINASE-ACTIVITY; DOWN-REGULATION; OVARIAN-CANCER; BREAST-CANCER; DIFFERENTIATION; PROLIFERATION research-areas: Biochemistry & Molecular Biology; Immunology web-of-science-categories: Biochemistry & Molecular Biology; Immunology author-email: [email protected] researcherid-numbers: Farzaneh, Farzin/B-4902-2009 orcid-numbers: Farzaneh, Farzin/0000-0002-9275-2415 Maher, John/0000-0001-8275-8488 number-of-cited-references: 57 times-cited: 12 usage-count-last-180-days: 0 usage-count-since-2013: 1 journal-iso: Mol. Immunol. doc-delivery-number: 260SF unique-id: ISI:000253030000009 da: 2018-08-30
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume45
pubs.embargo.termsNot known
dc.contributor.icrauthorRhiannon-Taylor, Jessicaen


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