Schilling, Hannah-Lou and Glehr, Gunther and Kapinsky, Michael and Ahrens, Norbert and Riquelme, Paloma and Cordero, Laura and Bitterer, Florian and Schlitt, Hans J. and Geissler, Edward K. and Haferkamp, Sebastian and Hutchinson, James A. and Kronenberg, Katharina (2021) Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications. FRONTIERS IN IMMUNOLOGY, 12: 765644. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
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 (T-EM) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given alpha PD-1 and alpha CTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4(+) T-EM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4(+) T-EM cells (agreement = 98%) and is superior in resolving CD4(+) CD197(+) CD45RA(-) central memory T cells (T-CM) from CD4(+) CD197(+) CD45RA(+) naive T cells (T-naive). 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELLS; COMBINED NIVOLUMAB; ADVERSE EVENTS; IPILIMUMAB; MELANOMA; VALIDATION; SURVIVAL; flow cytometry; assay validation; immune checkpoint inhibition; immune-related adverse events; prediction; effector memory T cells; monocytes; biomarker |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Informatics and Data Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jul 2022 07:13 |
| Last Modified: | 12 Jul 2022 07:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45716 |
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