{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["DePasquale EAK"],"funding":["Ludwig Center at Harvard","Fondation Bertarelli","American Foundation for Aging Research","Glenn Foundation for Medical Research","Mark Foundation For Cancer Research","National Cancer Institute","NCI NIH HHS","National Institutes of Health","Damon Runyon Cancer Research Foundation","Gilead Sciences","Leukemia and Lymphoma Society"],"pagination":["809414"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8960171"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13"],"pubmed_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 <i>via</i> 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."],"journal":["Frontiers in immunology"],"pubmed_title":["Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm."],"pmcid":["PMC8960171"],"funding_grant_id":["R00 CA218832","R37 CA225191"],"pubmed_authors":["van Galen P","Couturier CP","Lane AA","DePasquale EAK","Ainciburu M","Mallidi HR","Ssozi D","Shalek AK","Griffin GK","Noel J","Villanueva MA","Aranki SF","Good J"],"additional_accession":[]},"is_claimable":false,"name":"Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm.","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 <i>via</i> 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022","modification":"2026-05-31T21:01:19.532Z","creation":"2025-02-19T04:22:13.493Z"},"accession":"S-EPMC8960171","cross_references":{"pubmed":["35359938"],"doi":["10.3389/fimmu.2022.809414"]}}