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

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Liu, Xiangjun 
Hu, Simeng 
Li, Ruoyan 
Pan, Haihao 

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.


Funder: National Nature Science Foundation of China 81922058 National Science and Technology Major Project 2019YFC1315702 Guangdong Province Key Research and Development Program 2019B020226002 National Youth Top-Notch Talent Support Program 283812 Peking University Clinical Medicine plus X Youth Project PKU2019LCXQ012

Article, /631/250/580, /692/4028/67/1813, /692/4028/67/2329, /692/420/755, /631/67/1990/291/1621/1916, /49/91, article
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Nat Commun
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Springer Science and Business Media LLC