Phenotypic Plasticity of Malignant T Cells in Blood and Skin of a Sézary Syndrome Patient Revealed by Single Cell Transcriptomics

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Feb 10

PMID 36761972

Authors

Lukas Peiffer

Thilo Gambichler

Terkild B Buus

Kai Horny

Jan Gravemeyer

Frauke Furtmann

Ivelina Spassova

Linda Kubat

Laura Susok

Rene Stranzenbach

Nalini Srinivas

Niels Odum

Jurgen C Becker

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Objective: To compare the transcriptome of single cells in blood and skin samples from a patient with advanced SS.

Methods: We utilized combined single cell RNA and T-cell receptor (TCR) sequencing (scRNA-seq).

Results: 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 , and . 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 and . Pseudotime analysis indicated crucial transcriptomic changes in the transition of malignant T cells between blood and skin. These changes included the differential regulation of , 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.

Conclusions: 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.

Citing Articles

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