Effect of pembrolizumab on CD4 + CD25 + , CD4 + LAP + and CD4 + TIM-3 + T cell subsets

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Abstract

Tumor immune evasion involves the expansion of avidly proliferating immunosuppressive cells and inhibition of effector T cell proliferation. Immune checkpoints (IC) block the activation pathways of tumor-reactive T cells. IC pathways are often exploited by tumor cells to evade immune destruction, and blocking these pathways through IC inhibitors (ICI) has shown promising results in multiple malignancies. In this study, we investigated the effects of an ICI, pembrolizumab, on various T cell subsets in vitro. We compared the suppressive activity of CD4 + CD25 + regulatory T cells (conventional T reg ) with T cells expressing T cell immunoglobulin-3 + (TIM-3 + ) and latency-associated peptide (LAP) + T cells. We found that LAP-expressing T cells were more suppressive than conventional T reg , but TIM-3-expressing T cells were not suppressive. Our results show that pembrolizumab does not modulate functions of T reg and mediates its immunostimulatory effects via the release of effector T cells from suppression. These findings may assist in the development of agents designed to intervene in IC pathways to overcome T reg resistance to ICI.

Original languageEnglish
JournalClinical and Experimental Immunology
DOIs
Publication statusPublished - 1 Jan 2019

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T-Lymphocyte Subsets
T-Lymphocytes
Peptides
Peptide T
Tumor Escape
Neoplasms
pembrolizumab
Regulatory T-Lymphocytes
Immunosuppressive Agents
Immunoglobulins
Cell Proliferation

Keywords

  • cell activation
  • cell proliferation
  • regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Effect of pembrolizumab on CD4 + CD25 + , CD4 + LAP + and CD4 + TIM-3 + T cell subsets",
abstract = "Tumor immune evasion involves the expansion of avidly proliferating immunosuppressive cells and inhibition of effector T cell proliferation. Immune checkpoints (IC) block the activation pathways of tumor-reactive T cells. IC pathways are often exploited by tumor cells to evade immune destruction, and blocking these pathways through IC inhibitors (ICI) has shown promising results in multiple malignancies. In this study, we investigated the effects of an ICI, pembrolizumab, on various T cell subsets in vitro. We compared the suppressive activity of CD4 + CD25 + regulatory T cells (conventional T reg ) with T cells expressing T cell immunoglobulin-3 + (TIM-3 + ) and latency-associated peptide (LAP) + T cells. We found that LAP-expressing T cells were more suppressive than conventional T reg , but TIM-3-expressing T cells were not suppressive. Our results show that pembrolizumab does not modulate functions of T reg and mediates its immunostimulatory effects via the release of effector T cells from suppression. These findings may assist in the development of agents designed to intervene in IC pathways to overcome T reg resistance to ICI.",
keywords = "cell activation, cell proliferation, regulatory T cells",
author = "Muhammd Toor and Varun Nair and G. Pfister and Eyad Elkord",
year = "2019",
month = "1",
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doi = "10.1111/cei.13264",
language = "English",
journal = "Clinical and Experimental Immunology",
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T1 - Effect of pembrolizumab on CD4 + CD25 + , CD4 + LAP + and CD4 + TIM-3 + T cell subsets

AU - Toor, Muhammd

AU - Nair, Varun

AU - Pfister, G.

AU - Elkord, Eyad

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Tumor immune evasion involves the expansion of avidly proliferating immunosuppressive cells and inhibition of effector T cell proliferation. Immune checkpoints (IC) block the activation pathways of tumor-reactive T cells. IC pathways are often exploited by tumor cells to evade immune destruction, and blocking these pathways through IC inhibitors (ICI) has shown promising results in multiple malignancies. In this study, we investigated the effects of an ICI, pembrolizumab, on various T cell subsets in vitro. We compared the suppressive activity of CD4 + CD25 + regulatory T cells (conventional T reg ) with T cells expressing T cell immunoglobulin-3 + (TIM-3 + ) and latency-associated peptide (LAP) + T cells. We found that LAP-expressing T cells were more suppressive than conventional T reg , but TIM-3-expressing T cells were not suppressive. Our results show that pembrolizumab does not modulate functions of T reg and mediates its immunostimulatory effects via the release of effector T cells from suppression. These findings may assist in the development of agents designed to intervene in IC pathways to overcome T reg resistance to ICI.

AB - Tumor immune evasion involves the expansion of avidly proliferating immunosuppressive cells and inhibition of effector T cell proliferation. Immune checkpoints (IC) block the activation pathways of tumor-reactive T cells. IC pathways are often exploited by tumor cells to evade immune destruction, and blocking these pathways through IC inhibitors (ICI) has shown promising results in multiple malignancies. In this study, we investigated the effects of an ICI, pembrolizumab, on various T cell subsets in vitro. We compared the suppressive activity of CD4 + CD25 + regulatory T cells (conventional T reg ) with T cells expressing T cell immunoglobulin-3 + (TIM-3 + ) and latency-associated peptide (LAP) + T cells. We found that LAP-expressing T cells were more suppressive than conventional T reg , but TIM-3-expressing T cells were not suppressive. Our results show that pembrolizumab does not modulate functions of T reg and mediates its immunostimulatory effects via the release of effector T cells from suppression. These findings may assist in the development of agents designed to intervene in IC pathways to overcome T reg resistance to ICI.

KW - cell activation

KW - cell proliferation

KW - regulatory T cells

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