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

Muhammd Toor, A. S. Syed Khaja, I. Alkurd, Eyad Elkord

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Programmed death-1 (PD-1) and interactions with PD-ligand 1 (PD-L1) play critical roles in the tumour evasion of immune responses through different mechanisms, including inhibition of effector T cell proliferation, reducing cytotoxic activity, induction of apoptosis in tumour-infiltrating T cells and regulatory T cell (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 cytotoxic T lymphocyte antigen-4 (CTLA-4), CD15s, latency-associated peptide (LAP) and Ki-67. Moreover, we report that CD15s is expressed mainly on forkhead box P3 (FoxP3)Helios+ Treg in HD, but it is expressed on FoxP3+Helios Treg subset in addition to FoxP3Helios+ 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 signalling via the PD-1/PD-L1 axis in activated T cells.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalClinical and Experimental Immunology
Volume191
Issue number2
DOIs
Publication statusPublished - 1 Jan 2018

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Keywords

  • cancer
  • regulatory T cells
  • T cells
  • tumour immunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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