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Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm

The immune system represents a major barrier to cancer progression, driving the evolution of immunoregulatory interactions between malignant cells and T-cells in the tumor environment. Blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare acute leukemia with plasmacytoid dendritic cell (pDC)...

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Autores principales: DePasquale, Erica A. K., Ssozi, Daniel, Ainciburu, Marina, Good, Jonathan, Noel, Jenny, Villanueva, Martin A., Couturier, Charles P., Shalek, Alex K., Aranki, Sary F., Mallidi, Hari R., Griffin, Gabriel K., Lane, Andrew A., van Galen, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960171/
https://www.ncbi.nlm.nih.gov/pubmed/35359938
http://dx.doi.org/10.3389/fimmu.2022.809414
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author DePasquale, Erica A. K.
Ssozi, Daniel
Ainciburu, Marina
Good, Jonathan
Noel, Jenny
Villanueva, Martin A.
Couturier, Charles P.
Shalek, Alex K.
Aranki, Sary F.
Mallidi, Hari R.
Griffin, Gabriel K.
Lane, Andrew A.
van Galen, Peter
author_facet DePasquale, Erica A. K.
Ssozi, Daniel
Ainciburu, Marina
Good, Jonathan
Noel, Jenny
Villanueva, Martin A.
Couturier, Charles P.
Shalek, Alex K.
Aranki, Sary F.
Mallidi, Hari R.
Griffin, Gabriel K.
Lane, Andrew A.
van Galen, Peter
author_sort DePasquale, Erica A. K.
collection PubMed
description The immune system represents a major barrier to cancer progression, driving the evolution of immunoregulatory interactions between malignant cells and T-cells in the tumor environment. Blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare acute leukemia with plasmacytoid dendritic cell (pDC) differentiation, provides a unique opportunity to study these interactions. pDCs are key producers of interferon alpha (IFNA) that play an important role in T-cell activation at the interface between the innate and adaptive immune system. To assess how uncontrolled proliferation of malignant BPDCN cells affects the tumor environment, we catalog immune cell heterogeneity in the bone marrow (BM) of five healthy controls and five BPDCN patients by analyzing 52,803 single-cell transcriptomes, including 18,779 T-cells. We test computational techniques for robust cell type classification and find that T-cells in BPDCN patients consistently upregulate interferon alpha (IFNA) response and downregulate tumor necrosis factor alpha (TNFA) pathways. Integrating transcriptional data with T-cell receptor sequencing via shared barcodes reveals significant T-cell exhaustion in BPDCN that is positively correlated with T-cell clonotype expansion. By highlighting new mechanisms of T-cell exhaustion and immune evasion in BPDCN, our results demonstrate the value of single-cell multiomics to understand immune cell interactions in the tumor environment.
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spelling pubmed-89601712022-03-30 Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm DePasquale, Erica A. K. Ssozi, Daniel Ainciburu, Marina Good, Jonathan Noel, Jenny Villanueva, Martin A. Couturier, Charles P. Shalek, Alex K. Aranki, Sary F. Mallidi, Hari R. Griffin, Gabriel K. Lane, Andrew A. van Galen, Peter Front Immunol Immunology The immune system represents a major barrier to cancer progression, driving the evolution of immunoregulatory interactions between malignant cells and T-cells in the tumor environment. Blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare acute leukemia with plasmacytoid dendritic cell (pDC) differentiation, provides a unique opportunity to study these interactions. pDCs are key producers of interferon alpha (IFNA) that play an important role in T-cell activation at the interface between the innate and adaptive immune system. To assess how uncontrolled proliferation of malignant BPDCN cells affects the tumor environment, we catalog immune cell heterogeneity in the bone marrow (BM) of five healthy controls and five BPDCN patients by analyzing 52,803 single-cell transcriptomes, including 18,779 T-cells. We test computational techniques for robust cell type classification and find that T-cells in BPDCN patients consistently upregulate interferon alpha (IFNA) response and downregulate tumor necrosis factor alpha (TNFA) pathways. Integrating transcriptional data with T-cell receptor sequencing via shared barcodes reveals significant T-cell exhaustion in BPDCN that is positively correlated with T-cell clonotype expansion. By highlighting new mechanisms of T-cell exhaustion and immune evasion in BPDCN, our results demonstrate the value of single-cell multiomics to understand immune cell interactions in the tumor environment. Frontiers Media S.A. 2022-03-10 /pmc/articles/PMC8960171/ /pubmed/35359938 http://dx.doi.org/10.3389/fimmu.2022.809414 Text en Copyright © 2022 DePasquale, Ssozi, Ainciburu, Good, Noel, Villanueva, Couturier, Shalek, Aranki, Mallidi, Griffin, Lane and van Galen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
DePasquale, Erica A. K.
Ssozi, Daniel
Ainciburu, Marina
Good, Jonathan
Noel, Jenny
Villanueva, Martin A.
Couturier, Charles P.
Shalek, Alex K.
Aranki, Sary F.
Mallidi, Hari R.
Griffin, Gabriel K.
Lane, Andrew A.
van Galen, Peter
Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm
title Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm
title_full Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm
title_fullStr Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm
title_full_unstemmed Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm
title_short Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm
title_sort single-cell multiomics reveals clonal t-cell expansions and exhaustion in blastic plasmacytoid dendritic cell neoplasm
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960171/
https://www.ncbi.nlm.nih.gov/pubmed/35359938
http://dx.doi.org/10.3389/fimmu.2022.809414
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