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@ARTICLE{Peiffer:267543,
author = {L. Peiffer$^*$ and T. Gambichler and T. B. Buus and K.
Horny$^*$ and J. Gravemeyer$^*$ and F. Furtmann and I.
Spassova$^*$ and L. Kubat$^*$ and L. Susok and R.
Stranzenbach and N. Srinivas$^*$ and N. Ødum and J. C.
Becker$^*$},
title = {{P}henotypic plasticity of malignant {T} cells in blood and
skin of a {S}ézary syndrome patient revealed by single cell
transcriptomics.},
journal = {Frontiers in oncology},
volume = {13},
issn = {2234-943X},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2023-00321},
pages = {1090592},
year = {2023},
abstract = {Sézary Syndrome (SS) is an aggressive leukemic variant of
cutaneous T-cell lymphomas (CTCL). In SS patients, malignant
T cells are circulating through the blood and cause
erythroderma.To compare the transcriptome of single cells in
blood and skin samples from a patient with advanced SS.We
utilized combined single cell RNA and T-cell receptor (TCR)
sequencing (scRNA-seq).We scrutinized the malignant T cells
in blood and skin in an unbiased manner without pre-sorting
of cells. We observed different phenotypes of the same
monoclonal malignant T-cell population, confirmed by TCR
sequencing and inferred copy number variation analysis.
Malignant T cells present in the circulating blood expressed
genes resembling central memory T cells such as CCR7, IL7R
and CD27. In the skin, we detected two major malignant
T-cell populations: One subpopulation was closely related to
the malignant T cells from the blood, while the other
subpopulation expressed genes reminiscent of skin resident
effector memory T cells including GZMB and NKG7. Pseudotime
analysis indicated crucial transcriptomic changes in the
transition of malignant T cells between blood and skin.
These changes included the differential regulation of TXNIP,
a putative tumor suppressor in CTCL, and the adaptation to
the hypoxic conditions in the skin. Tumor cell proliferation
in the skin was supported by stimulating interactions
between myeloid cells and malignant T cells.Using scRNA-seq
we detected a high degree of functional heterogeneity within
the malignant T-cell population in SS and highlighted
crucial differences between SS cells in blood and skin.},
keywords = {Sézary syndrome (Other) / cutaneous T cell lymphoma
(Other) / inflammation (Other) / malignant T cells (Other) /
reactive T cells (Other) / scRNAseq (Other)},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36761972},
pmc = {pmc:PMC9905421},
doi = {10.3389/fonc.2023.1090592},
url = {https://inrepo02.dkfz.de/record/267543},
}