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Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells

Khan, S, Burt, D, Ralph, C, Hawkins, R and Elkord, E 2011, 'Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells' , Clinical Immunology, 138 (1) , pp. 85-96.

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    Abstract

    Cytotoxic T Lymphocyte Antigen 4 (CTLA4) blockade has shown antitumor activity against common cancers. However, the exact mechanism of immune mediation by anti-CTLA4 remains to be elucidated. Further understanding of how CTLA4 blockade with tremelimumab mediates immune responses may allow a more effective selection of responsive patients. Our results show that tremelimumab enhanced the proliferative response of T effector cells (Teff) upon TCR stimulation, and abrogated Treg suppressive ability. In the presence of tremelimumab, frequencies of IL-2-secreting CD4(+) T cells and IFN-γ-secreting CD4(+) and CD8(+) T cells were increased in response to polyclonal activation and tumor antigens. Importantly, Treg frequency was not reduced in the presence of tremelimumab, and expanded Tregs in cancer patients treated with tremelimumab expressed FoxP3 with no IL-2 release, confirming them as bona fide Tregs. Taken together, this data indicates that tremelimumab induces immune responses mainly by direct activation of Teff rather than by affecting Tregs.

    Item Type: Article
    Themes: Health and Wellbeing
    Schools: Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences > Biomedical Research Centre
    Journal or Publication Title: Clinical Immunology
    Publisher: Elsevier
    Refereed: Yes
    ISSN: 1521-6616
    Depositing User: E Elkord
    Date Deposited: 11 Oct 2011 16:23
    Last Modified: 20 Aug 2013 18:13
    URI: http://usir.salford.ac.uk/id/eprint/18230

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