Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm
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fimmu-13-809414.pdf
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Published version
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Author(s)
DePasquale, Erica AK
Ssozi, Daniel
Ainciburu, Marina
Good, Jonathan
Noel, Jenny
Villanueva, Martin A
Couturier, Charles P
Shalek, Alex K
Aranki, Sary F
Mallidi, Hari R
Date Issued
March 10, 2022
Journal
Frontiers in Immunology
Publisher
Frontiers Media SA
Citation
DePasquale EAK, Ssozi D, Ainciburu M, Good J, Noel J, Villanueva MA, Couturier CP, Shalek AK, Aranki SF, Mallidi HR, Griffin GK, Lane AA and van Galen P (2022) Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm. Front. Immunol. 13:809414.
Version
Final published version
Abstract
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.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.3389/fimmu.2022.809414
