In vitro effect of pembrolizumab on different T regulatory cell subsets.
AffiliationCancer Research Center, Qatar Biomedical Research Institute, College of Science and Engineering, Hamad Bin Khalifa University, Qatar Foundation, Doha,
MetadataShow full item record
AbstractProgrammed 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.
CitationIn vitro effect of pembrolizumab on different T regulatory cell subsets. 2017, Clin Exp Immunol
JournalClinical and Experimental Immunology
- Immune suppression in premalignant respiratory papillomas: enriched functional CD4+Foxp3+ regulatory T cells and PD-1/PD-L1/L2 expression.
- Authors: Hatam LJ, Devoti JA, Rosenthal DW, Lam F, Abramson AL, Steinberg BM, Bonagura VR
- Issue date: 2012 Apr 1
- Staphylococcus aureus convert neonatal conventional CD4(+) T cells into FOXP3(+) CD25(+) CD127(low) T cells via the PD-1/PD-L1 axis.
- Authors: Rabe H, Nordström I, Andersson K, Lundell AC, Rudin A
- Issue date: 2014 Mar
- Pembrolizumab Interferes with the Differentiation of Human FOXP3<sup>+</sup>-Induced T Regulatory Cells, but Not with FOXP3 Stability, through Activation of mTOR.
- Authors: Sasidharan Nair V, Toor SM, Taouk G, Pfister G, Ouararhni K, Alajez NM, Elkord E
- Issue date: 2020 Jan 1
- Preferential accumulation of regulatory T cells with highly immunosuppressive characteristics in breast tumor microenvironment.
- Authors: Syed Khaja AS, Toor SM, El Salhat H, Faour I, Ul Haq N, Ali BR, Elkord E
- Issue date: 2017 May 16
- Effect of pembrolizumab on CD4<sup>+</sup> CD25<sup>+</sup> , CD4<sup>+</sup> LAP<sup>+</sup> and CD4<sup>+</sup> TIM-3<sup>+</sup> T cell subsets.
- Authors: Toor SM, Sasidharan Nair V, Pfister G, Elkord E
- Issue date: 2019 Jun