FlowCT for the analysis of large immunophenotypic data sets and biomarker discovery in cancer immunology
Large-scale immune monitoring is becoming routinely used in clinical trials to identify determinants of treatment responsiveness, particularly to immunotherapies. Flow cytometry remains one of the most versatile and high throughput approaches for single-cell analysis; however, manual interpretation...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 January 2022
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| In: |
Blood advances
Year: 2022, Volume: 6, Issue: 2, Pages: 690-703 |
| ISSN: | 2473-9537 |
| DOI: | 10.1182/bloodadvances.2021005198 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/bloodadvances.2021005198
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| Author Notes: | Cirino Botta, Catarina Maia, Juan-José Garcés, Rosalinda Termini, Cristina Perez, Irene Manrique, Leire Burgos, Aintzane Zabaleta, Diego Alignani, Sarai Sarvide, Juana Merino, Noemi Puig, María-Teresa Cedena, Marco Rossi, Pierfrancesco Tassone, Massimo Gentile, Pierpaolo Correale, Ivan Borrello, Evangelos Terpos, Tomas Jelinek, Artur Paiva, Aldo Roccaro, Hartmut Goldschmidt, Hervé Avet-Loiseau, Laura Rosinol, Maria-Victoria Mateos, Joaquin Martinez-Lopez, Juan-José Lahuerta, Joan Bladé, Jesús F. San-Miguel, and Bruno Paiva, on behalf of the Programa Para el Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) cooperative group and the iMMunocell study group |
| Summary: | Large-scale immune monitoring is becoming routinely used in clinical trials to identify determinants of treatment responsiveness, particularly to immunotherapies. Flow cytometry remains one of the most versatile and high throughput approaches for single-cell analysis; however, manual interpretation of multidimensional data poses a challenge when attempting to capture full cellular diversity and provide reproducible results. We present FlowCT, a semi-automated workspace empowered to analyze large data sets. It includes pre-processing, normalization, multiple dimensionality reduction techniques, automated clustering, and predictive modeling tools. As a proof of concept, we used FlowCT to compare the T-cell compartment in bone marrow (BM) with peripheral blood (PB) from patients with smoldering multiple myeloma (SMM), identify minimally invasive immune biomarkers of progression from smoldering to active MM, define prognostic T-cell subsets in the BM of patients with active MM after treatment intensification, and assess the longitudinal effect of maintenance therapy in BM T cells. A total of 354 samples were analyzed and immune signatures predictive of malignant transformation were identified in 150 patients with SMM (hazard ratio [HR], 1.7; P < .001). We also determined progression-free survival (HR, 4.09; P < .0001) and overall survival (HR, 3.12; P = .047) in 100 patients with active MM. New data also emerged about stem cell memory T cells, the concordance between immune profiles in BM and PB, and the immunomodulatory effect of maintenance therapy. FlowCT is a new open-source computational approach that can be readily implemented by research laboratories to perform quality control, analyze high-dimensional data, unveil cellular diversity, and objectively identify biomarkers in large immune monitoring studies. These trials were registered at www.clinicaltrials.gov as #NCT01916252 and #NCT02406144. |
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| Item Description: | Gesehen am 25.03.2022 |
| Physical Description: | Online Resource |
| ISSN: | 2473-9537 |
| DOI: | 10.1182/bloodadvances.2021005198 |