[HTML][HTML] Single-cell transcriptomics links malignant T cells to the tumor immune landscape in cutaneous T cell lymphoma

X Liu, S Jin, S Hu, R Li, H Pan, Y Liu, P Lai, D Xu… - Nature …, 2022 - nature.com
X Liu, S Jin, S Hu, R Li, H Pan, Y Liu, P Lai, D Xu, J Sun, Z Liu, Y Gao, Y Zhao, F Liu, Y Xiao…
Nature communications, 2022nature.com
Cutaneous T cell lymphoma (CTCL) represents a heterogeneous group of non-Hodgkin
lymphoma distinguished by the presence of clonal malignant T cells. The heterogeneity of
malignant T cells and the complex tumor microenvironment remain poorly characterized.
With single-cell RNA analysis and bulk whole-exome sequencing on 19 skin lesions from 15
CTCL patients, we decipher the intra-tumor and inter-lesion diversity of CTCL patients and
propose a multi-step tumor evolution model. We further establish a subtyping scheme based …
Abstract
Cutaneous T cell lymphoma (CTCL) represents a heterogeneous group of non-Hodgkin lymphoma distinguished by the presence of clonal malignant T cells. The heterogeneity of malignant T cells and the complex tumor microenvironment remain poorly characterized. With single-cell RNA analysis and bulk whole-exome sequencing on 19 skin lesions from 15 CTCL patients, we decipher the intra-tumor and inter-lesion diversity of CTCL patients and propose a multi-step tumor evolution model. We further establish a subtyping scheme based on the molecular features of malignant T cells and their pro-tumorigenic microenvironments: the TCyEM group, demonstrating a cytotoxic effector memory T cell phenotype, shows more M2 macrophages infiltration, while the TCM group, featured by a central memory T cell phenotype and adverse patient outcome, is infiltrated by highly exhausted CD8+ reactive T cells, B cells and Tregs with suppressive activities. Our results establish a solid basis for understanding the nature of CTCL and pave the way for future precision medicine for CTCL patients.
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