Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications

Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-...

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Autores principales:	Hannah-Lou Schilling, Gunther Glehr, Michael Kapinsky, Norbert Ahrens, Paloma Riquelme, Laura Cordero, Florian Bitterer, Hans J. Schlitt, Edward K. Geissler, Sebastian Haferkamp, James A. Hutchinson, Katharina Kronenberg
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	flow cytometry assay validation immune checkpoint inhibition immune-related adverse events prediction effector memory T cells Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/978480e0f0484366a2e24632235b94b1
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spelling	oai:doaj.org-article:978480e0f0484366a2e24632235b94b12021-11-16T07:47:40ZDevelopment of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications1664-322410.3389/fimmu.2021.765644https://doaj.org/article/978480e0f0484366a2e24632235b94b12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.765644/fullhttps://doaj.org/toc/1664-3224Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4+ effector memory T cells (TEM) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given αPD-1 and αCTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4+ TEM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4+ TEM cells (agreement = 98%) and is superior in resolving CD4+ CD197+ CD45RA- central memory T cells (TCM) from CD4+ CD197+ CD45RA+ naive T cells (Tnaive). It also enables us to precisely quantify CD14+ monocytes (CV = 6.6%). Our new “monocyte and T cell” (MoT) assay predicts immune-related hepatitis with a positive predictive value (PPV) of 83% and negative predictive value (NPV) of 80%. Our essential improvements open the possibility of sharing our predictive methods with other clinical centers. Furthermore, condensing measurements of monocyte and memory T cell subsets into a single assay simplifies our workflows and facilitates computational analyses.Hannah-Lou SchillingGunther GlehrMichael KapinskyNorbert AhrensNorbert AhrensPaloma RiquelmeLaura CorderoFlorian BittererHans J. SchlittEdward K. GeisslerSebastian HaferkampJames A. HutchinsonKatharina KronenbergFrontiers Media S.A.articleflow cytometryassay validationimmune checkpoint inhibitionimmune-related adverse eventspredictioneffector memory T cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	flow cytometry assay validation immune checkpoint inhibition immune-related adverse events prediction effector memory T cells Immunologic diseases. Allergy RC581-607
spellingShingle	flow cytometry assay validation immune checkpoint inhibition immune-related adverse events prediction effector memory T cells Immunologic diseases. Allergy RC581-607 Hannah-Lou Schilling Gunther Glehr Michael Kapinsky Norbert Ahrens Norbert Ahrens Paloma Riquelme Laura Cordero Florian Bitterer Hans J. Schlitt Edward K. Geissler Sebastian Haferkamp James A. Hutchinson Katharina Kronenberg Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications
description	Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4+ effector memory T cells (TEM) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given αPD-1 and αCTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4+ TEM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4+ TEM cells (agreement = 98%) and is superior in resolving CD4+ CD197+ CD45RA- central memory T cells (TCM) from CD4+ CD197+ CD45RA+ naive T cells (Tnaive). It also enables us to precisely quantify CD14+ monocytes (CV = 6.6%). Our new “monocyte and T cell” (MoT) assay predicts immune-related hepatitis with a positive predictive value (PPV) of 83% and negative predictive value (NPV) of 80%. Our essential improvements open the possibility of sharing our predictive methods with other clinical centers. Furthermore, condensing measurements of monocyte and memory T cell subsets into a single assay simplifies our workflows and facilitates computational analyses.
format	article
author	Hannah-Lou Schilling Gunther Glehr Michael Kapinsky Norbert Ahrens Norbert Ahrens Paloma Riquelme Laura Cordero Florian Bitterer Hans J. Schlitt Edward K. Geissler Sebastian Haferkamp James A. Hutchinson Katharina Kronenberg
author_facet	Hannah-Lou Schilling Gunther Glehr Michael Kapinsky Norbert Ahrens Norbert Ahrens Paloma Riquelme Laura Cordero Florian Bitterer Hans J. Schlitt Edward K. Geissler Sebastian Haferkamp James A. Hutchinson Katharina Kronenberg
author_sort	Hannah-Lou Schilling
title	Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications
title_short	Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications
title_full	Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications
title_fullStr	Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications
title_full_unstemmed	Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications
title_sort	development of a flow cytometry assay to predict immune checkpoint blockade-related complications
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/978480e0f0484366a2e24632235b94b1
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Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications

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