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

Xiangjun Liu, Shanzhao Jin, Simeng Hu, Ruoyan Li, Haihao Pan, Yi Liu, Pan Lai, Deshu Xu, Jingru Sun, Ziyang Liu, Yumei Gao, Yifan Zhao, Fengjie Liu, Yu Xiao, Yingyi Li, Yujie Wen, Zhuojing Chen, Bufang Xu, Yuchieh Lin, Menglong Ran, Qianxi Li, Shuxia Yang, Hang Li, Ping Tu, Muzlifah Haniffa, Sarah A. Teichmann, Fan Bai () and Yang Wang ()
Additional contact information
Xiangjun Liu: Peking University First Hospital
Shanzhao Jin: Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University
Simeng Hu: Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University
Ruoyan Li: Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University
Haihao Pan: Peking University First Hospital
Yi Liu: Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University
Pan Lai: Peking University First Hospital
Deshu Xu: Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University
Jingru Sun: Peking University First Hospital
Ziyang Liu: Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University
Yumei Gao: Peking University First Hospital
Yifan Zhao: Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University
Fengjie Liu: Peking University First Hospital
Yu Xiao: Peking University First Hospital
Yingyi Li: Peking University First Hospital
Yujie Wen: Peking University First Hospital
Zhuojing Chen: Peking University First Hospital
Bufang Xu: Peking University First Hospital
Yuchieh Lin: Peking University First Hospital
Menglong Ran: Peking University First Hospital
Qianxi Li: Peking University First Hospital
Shuxia Yang: Peking University First Hospital
Hang Li: Peking University First Hospital
Ping Tu: Peking University First Hospital
Muzlifah Haniffa: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Sarah A. Teichmann: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Fan Bai: Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University
Yang Wang: Peking University First Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28799-3

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