Single-Cell RNA-seq Reveals Characteristics of Malignant Cells and Immune Microenvironment in Subcutaneous Panniculitis-Like T-Cell Lymphoma

单细胞 RNA 测序揭示皮下脂膜炎样 T 细胞淋巴瘤中恶性细胞和免疫微环境的特征

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作者:Zifeng Li, Hongsheng Wang, Rui Dong, Jie Man, Li Sun, Xiaowen Qian, Xiaohua Zhu, Ping Cao, Yi Yu, Jun Le, Yang Fu, Ping Wang, Wenjin Jiang, Chen Shen, Yangyang Ma, Lian Chen, Yaochen Xu, Jiantao Shi, Hui Zhang, Maoxiang Qian, Xiaowen Zhai

Background

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary T-cell lymphoma that is challenging to distinguish from autoimmune disorders and reactive panniculitides. Delay in diagnosis and a high misdiagnosis rate affect the prognosis and survival of patients. The difficulty of diagnosis is mainly due to an incomplete understanding of disease pathogenesis.

Conclusions

This work offers insight into the heterogeneity of subcutaneous panniculitis-like T-cell lymphoma, providing a better understanding of the transcription characteristics and immune microenvironment of this rare tumor.

Methods

We performed single-cell RNA sequencing of matched subcutaneous lesion tissue, peripheral blood, and bone marrow from a patient with SPTCL, as well as peripheral blood, bone marrow, lymph node, and lung tissue samples from healthy donors as normal controls. We conducted cell clustering, gene expression program identification, gene differential expression analysis, and cell-cell interaction analysis to investigate the ecosystem of SPTCL.

Results

Based on gene expression profiles in a single-cell resolution, we identified and characterized the malignant cells and immune subsets from a patient with SPTCL. Our analysis showed that SPTCL malignant cells expressed a distinct gene signature, including chemokines families, cytotoxic proteins, T cell immune checkpoint molecules, and the immunoglobulin family. By comparing with normal T cells, we identified potential novel markers for SPTCL (e.g., CYTOR, CXCL13, VCAM1, and TIMD4) specifically differentially expressed in the malignant cells. We also found that macrophages and fibroblasts dominated the cell-cell communication landscape with the SPTCL malignant cells. Conclusions: This work offers insight into the heterogeneity of subcutaneous panniculitis-like T-cell lymphoma, providing a better understanding of the transcription characteristics and immune microenvironment of this rare tumor.

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