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    In vitro effect of pembrolizumab on different T regulatory cell subsets.

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    Authors
    Toor, S
    Syed Khaja, A
    Alkurd, I
    Elkord, Eyad
    Affiliation
    Cancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha,
    Issue Date
    2017-09-30
    
    Metadata
    Show full item record
    Abstract
    Programmed death-1 (PD-1) and interactions with PD-L1 play critical roles in the tumor evasion of immune responses through different mechanisms including inhibition of effector T cell proliferation, reducing cytotoxic activity, induction of apoptosis in tumor-infiltrating T cells, and regulatory T cells (Treg) expansion. Effective blockade of immune checkpoints can therefore potentially eliminate these detrimental effects. The aim of this study was to investigate the effect of anti-PD-1 antibody, pembrolizumab, on various Treg subpopulations. Peripheral blood mononuclear cells (PBMC) from healthy donors (HD) and primary breast cancer patients (PBC) were treated in vitro with pembrolizumab, which effectively reduced PD-1 expression in both cohorts. We found that PD-1 was expressed mainly on CD4(+) CD25(+) T cells, and pembrolizumab had a greater effect on PD-1 expression in CD4(+) CD25(-) T cells, compared to CD4(+) CD25(+) cells. In addition, pembrolizumab did not affect the expression levels of Treg-related markers including CTLA-4, CD15s, LAP and Ki-67. Moreover, we report that CD15s is mainly expressed on FoxP3(-) Helios(+) Treg in HD, but it is expressed on FoxP3(+) Helios(-) Treg subset in addition to FoxP3(-) Helios(+) Treg in PBC. Pembrolizumab did not affect the levels of FoxP3(+/-) Helios(+/-) Treg subsets in both cohorts. Taken together, our study suggests that pembrolizumab does not affect Treg or change their phenotype or function but rather blocks signaling via PD-1/PD-L1 axis in activated T cells. This article is protected by copyright. All rights reserved.
    Citation
    In vitro effect of pembrolizumab on different T regulatory cell subsets. 2017, Clin Exp Immunol
    Journal
    Clinical and Experimental Immunology
    URI
    http://hdl.handle.net/10541/620604
    DOI
    10.1111/cei.13060
    PubMed ID
    28963773
    Type
    Article
    Language
    en
    ISSN
    1365-2249
    ae974a485f413a2113503eed53cd6c53
    10.1111/cei.13060
    Scopus Count
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    All Paterson Institute for Cancer Research

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