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Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy

The absence of reliable, robust, and non-invasive biomarkers for anti- Programmed cell death protein 1 (PD-1) immunotherapy is an urgent unmet medical need for the treatment of cancer patients. No predictive biomarkers have been established based on the direct assessment of T cell functions, the pri...

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Autores principales: Bacot, Silvia M., Harper, Taylor A., Matthews, Rebecca L., Fennell, Christie Jane, Akue, Adovi, KuKuruga, Mark A., Lee, Shiowjen, Wang, Tao, Feldman, Gerald M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730837/
https://www.ncbi.nlm.nih.gov/pubmed/33261003
http://dx.doi.org/10.3390/ijms21239023
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author Bacot, Silvia M.
Harper, Taylor A.
Matthews, Rebecca L.
Fennell, Christie Jane
Akue, Adovi
KuKuruga, Mark A.
Lee, Shiowjen
Wang, Tao
Feldman, Gerald M.
author_facet Bacot, Silvia M.
Harper, Taylor A.
Matthews, Rebecca L.
Fennell, Christie Jane
Akue, Adovi
KuKuruga, Mark A.
Lee, Shiowjen
Wang, Tao
Feldman, Gerald M.
author_sort Bacot, Silvia M.
collection PubMed
description The absence of reliable, robust, and non-invasive biomarkers for anti- Programmed cell death protein 1 (PD-1) immunotherapy is an urgent unmet medical need for the treatment of cancer patients. No predictive biomarkers have been established based on the direct assessment of T cell functions, the primary mechanism of action of anti-PD-1 therapy. In this study, we established a model system to test T cell functions modulated by Nivolumab using anti-CD3 monoclonal antibody (mAb)-stimulated peripheral blood mononuclear cells (PBMCs), and characterized T cell functions primarily based on the knowledge gained from retrospective observations of patients treated with anti-PD-1 immunotherapy. During a comprehensive cytokine profile assessment to identify potential biomarkers, we found that Nivolumab increases expression of T helper type 1 (Th1) associated cytokines such as interferon-γ (IFN-γ) and interleukin-2 (IL-2) in a subset of donors. Furthermore, Nivolumab increases production of Th2, Th9, and Th17 associated cytokines, as well as many proinflammatory cytokines such as IL-6 in a subset of donors. Conversely, Nivolumab treatment has no impact on T cell proliferation, expression of CD25, CD69, or Granzyme B, and only modestly increases in the expansion of regulatory T cells. Our results suggest that assessment of cytokine production using a simple PBMC-based T cell functional assay could be used as a potential predictive marker for anti-PD-1 immunotherapy.
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spelling pubmed-77308372020-12-12 Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy Bacot, Silvia M. Harper, Taylor A. Matthews, Rebecca L. Fennell, Christie Jane Akue, Adovi KuKuruga, Mark A. Lee, Shiowjen Wang, Tao Feldman, Gerald M. Int J Mol Sci Article The absence of reliable, robust, and non-invasive biomarkers for anti- Programmed cell death protein 1 (PD-1) immunotherapy is an urgent unmet medical need for the treatment of cancer patients. No predictive biomarkers have been established based on the direct assessment of T cell functions, the primary mechanism of action of anti-PD-1 therapy. In this study, we established a model system to test T cell functions modulated by Nivolumab using anti-CD3 monoclonal antibody (mAb)-stimulated peripheral blood mononuclear cells (PBMCs), and characterized T cell functions primarily based on the knowledge gained from retrospective observations of patients treated with anti-PD-1 immunotherapy. During a comprehensive cytokine profile assessment to identify potential biomarkers, we found that Nivolumab increases expression of T helper type 1 (Th1) associated cytokines such as interferon-γ (IFN-γ) and interleukin-2 (IL-2) in a subset of donors. Furthermore, Nivolumab increases production of Th2, Th9, and Th17 associated cytokines, as well as many proinflammatory cytokines such as IL-6 in a subset of donors. Conversely, Nivolumab treatment has no impact on T cell proliferation, expression of CD25, CD69, or Granzyme B, and only modestly increases in the expansion of regulatory T cells. Our results suggest that assessment of cytokine production using a simple PBMC-based T cell functional assay could be used as a potential predictive marker for anti-PD-1 immunotherapy. MDPI 2020-11-27 /pmc/articles/PMC7730837/ /pubmed/33261003 http://dx.doi.org/10.3390/ijms21239023 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bacot, Silvia M.
Harper, Taylor A.
Matthews, Rebecca L.
Fennell, Christie Jane
Akue, Adovi
KuKuruga, Mark A.
Lee, Shiowjen
Wang, Tao
Feldman, Gerald M.
Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy
title Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy
title_full Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy
title_fullStr Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy
title_full_unstemmed Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy
title_short Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy
title_sort exploring the potential use of a pbmc-based functional assay to identify predictive biomarkers for anti-pd-1 immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730837/
https://www.ncbi.nlm.nih.gov/pubmed/33261003
http://dx.doi.org/10.3390/ijms21239023
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