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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Vydané v:	International journal of molecular sciences Ročník 21; číslo 23; s. 9023
Hlavní autori:	Bacot, Silvia M., Harper, Taylor A., Matthews, Rebecca L., Fennell, Christie Jane, Akue, Adovi, KuKuruga, Mark A., Lee, Shiowjen, Wang, Tao, Feldman, Gerald M.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Switzerland MDPI AG 27.11.2020 MDPI
Predmet:	Antigens, CD - metabolism Biomarkers Biomarkers - metabolism Cancer Cell Proliferation - drug effects Cytokines Cytokines - biosynthesis Cytomegalovirus Deoxyribonucleic acid DNA FDA approval Flow cytometry Granzymes - metabolism Humans Immunoassay Immunotherapy Leukocytes, Mononuclear - metabolism Lymphocyte Activation - drug effects Lymphocytes Mutation Nivolumab - pharmacology Patients Programmed Cell Death 1 Receptor - metabolism T cell receptors T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Targeted cancer therapy Th1 Cells - immunology Tissue Donors peripheral blood mononuclear cells cytokines T cells biomarker Nivolumab
ISSN:	1422-0067, 1661-6596, 1422-0067
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Current address: Cancer ImmunoPrevention Laboratory, Vaccine, Immunity, and Cancer Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. Current address: Flow Cytometry Core Facility, School of Medicine, University of Virginia, Charlottesville, VA 22903, USA. These authors contributed equally to this paper.
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms21239023