Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks

Abstract The tissue microenvironment in chronic lymphocytic leukaemia (CLL) plays a key role in the pathogenesis of CLL, but the complex blood microenvironment in CLL has not yet been fully characterised. Therefore, immunophenotyping of circulating immune cells in 244 CLL patients and 52 healthy con...

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Autores principales: Zuzana Mikulkova, Gayane Manukyan, Peter Turcsanyi, Milos Kudelka, Renata Urbanova, Jakub Savara, Eliska Ochodkova, Yvona Brychtova, Jan Molinsky, Martin Simkovic, David Starostka, Jan Novak, Ondrej Janca, Martin Dihel, Pavlina Ryznerova, Lekaa Mohammad, Tomas Papajik, Eva Kriegova
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:def86669326e46929974b57867c486122021-12-02T15:22:56ZDeciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks10.1038/s41598-020-79121-42045-2322https://doaj.org/article/def86669326e46929974b57867c486122021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79121-4https://doaj.org/toc/2045-2322Abstract The tissue microenvironment in chronic lymphocytic leukaemia (CLL) plays a key role in the pathogenesis of CLL, but the complex blood microenvironment in CLL has not yet been fully characterised. Therefore, immunophenotyping of circulating immune cells in 244 CLL patients and 52 healthy controls was performed using flow cytometry and analysed by multivariate Patient Similarity Networks (PSNs). Our study revealed high inter-individual heterogeneity in the distribution and activation of bystander immune cells in CLL, depending on the bulk of the CLL cells. High CLL counts were associated with low activation on circulating monocytes and T cells and vice versa. The highest activation of immune cells, particularly of intermediate and non-classical monocytes, was evident in patients treated with novel agents. PSNs revealed a low activation of immune cells in CLL progression, irrespective of IgHV status, Binet stage and TP53 disruption. Patients with high intermediate monocytes (> 5.4%) with low activation were 2.5 times more likely (95% confidence interval 1.421–4.403, P = 0.002) to had shorter time-to-treatment than those with low monocyte counts. Our study demonstrated the association between the activation of circulating immune cells and the bulk of CLL cells. The highest activation of bystander immune cells was detected in patients with slow disease course and in those treated with novel agents. The subset of intermediate monocytes showed predictive value for time-to-treatment in CLL.Zuzana MikulkovaGayane ManukyanPeter TurcsanyiMilos KudelkaRenata UrbanovaJakub SavaraEliska OchodkovaYvona BrychtovaJan MolinskyMartin SimkovicDavid StarostkaJan NovakOndrej JancaMartin DihelPavlina RyznerovaLekaa MohammadTomas PapajikEva KriegovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Zuzana Mikulkova
Gayane Manukyan
Peter Turcsanyi
Milos Kudelka
Renata Urbanova
Jakub Savara
Eliska Ochodkova
Yvona Brychtova
Jan Molinsky
Martin Simkovic
David Starostka
Jan Novak
Ondrej Janca
Martin Dihel
Pavlina Ryznerova
Lekaa Mohammad
Tomas Papajik
Eva Kriegova
Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks
description Abstract The tissue microenvironment in chronic lymphocytic leukaemia (CLL) plays a key role in the pathogenesis of CLL, but the complex blood microenvironment in CLL has not yet been fully characterised. Therefore, immunophenotyping of circulating immune cells in 244 CLL patients and 52 healthy controls was performed using flow cytometry and analysed by multivariate Patient Similarity Networks (PSNs). Our study revealed high inter-individual heterogeneity in the distribution and activation of bystander immune cells in CLL, depending on the bulk of the CLL cells. High CLL counts were associated with low activation on circulating monocytes and T cells and vice versa. The highest activation of immune cells, particularly of intermediate and non-classical monocytes, was evident in patients treated with novel agents. PSNs revealed a low activation of immune cells in CLL progression, irrespective of IgHV status, Binet stage and TP53 disruption. Patients with high intermediate monocytes (> 5.4%) with low activation were 2.5 times more likely (95% confidence interval 1.421–4.403, P = 0.002) to had shorter time-to-treatment than those with low monocyte counts. Our study demonstrated the association between the activation of circulating immune cells and the bulk of CLL cells. The highest activation of bystander immune cells was detected in patients with slow disease course and in those treated with novel agents. The subset of intermediate monocytes showed predictive value for time-to-treatment in CLL.
format article
author Zuzana Mikulkova
Gayane Manukyan
Peter Turcsanyi
Milos Kudelka
Renata Urbanova
Jakub Savara
Eliska Ochodkova
Yvona Brychtova
Jan Molinsky
Martin Simkovic
David Starostka
Jan Novak
Ondrej Janca
Martin Dihel
Pavlina Ryznerova
Lekaa Mohammad
Tomas Papajik
Eva Kriegova
author_facet Zuzana Mikulkova
Gayane Manukyan
Peter Turcsanyi
Milos Kudelka
Renata Urbanova
Jakub Savara
Eliska Ochodkova
Yvona Brychtova
Jan Molinsky
Martin Simkovic
David Starostka
Jan Novak
Ondrej Janca
Martin Dihel
Pavlina Ryznerova
Lekaa Mohammad
Tomas Papajik
Eva Kriegova
author_sort Zuzana Mikulkova
title Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks
title_short Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks
title_full Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks
title_fullStr Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks
title_full_unstemmed Deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks
title_sort deciphering the complex circulating immune cell microenvironment in chronic lymphocytic leukaemia using patient similarity networks
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/def86669326e46929974b57867c48612
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