A single-cell atlas of diffuse large B cell lymphoma

Xiaofei Ye; Lei Wang; Man Nie; Yuyao Wang; Shichen Dong; Weicheng Ren; Guibo Li; Zhi-Ming Li; Kui Wu; Qiang Pan-Hammarström

doi:10.1016/j.celrep.2022.110713

A single-cell atlas of diffuse large B cell lymphoma

Cell Rep. 2022 Apr 19;39(3):110713. doi: 10.1016/j.celrep.2022.110713.

Authors

Xiaofei Ye¹, Lei Wang², Man Nie³, Yuyao Wang⁴, Shichen Dong⁴, Weicheng Ren¹, Guibo Li⁵, Zhi-Ming Li⁶, Kui Wu⁷, Qiang Pan-Hammarström⁸

Affiliations

¹ Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Stockholm, Sweden.
² BGI-Shenzhen, Shenzhen 518000, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI-Shenzhen, Shenzhen 518000, China.
³ Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
⁴ BGI-Shenzhen, Shenzhen 518000, China.
⁵ BGI-Shenzhen, Shenzhen 518000, China; Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen 518000, China.
⁶ Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: lizhm@sysucc.org.cn.
⁷ BGI-Shenzhen, Shenzhen 518000, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI-Shenzhen, Shenzhen 518000, China. Electronic address: wukui@genomics.cn.
⁸ Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Stockholm, Sweden. Electronic address: qiang.pan-hammarstrom@ki.se.

PMID: 35443163
DOI: 10.1016/j.celrep.2022.110713

Abstract

Diffuse large B cell lymphoma (DLBCL) is one of the most common yet aggressive types of B cell lymphoma and remains incurable in 40% of patients. Herein, we profile the transcriptomes of 94,324 cells from 17 DLBCLs and 3 control samples using single-cell RNA sequencing. Altogether, 73 gene expression programs are identified in malignant cells, demonstrating high intra- and intertumor heterogeneity. Furthermore, 2,754 pairs of suggestive cell-cell interactions are predicted, indicating a complex and highly dynamic tumor microenvironment. Especially for B cell lymphomas, a strong costimulatory CD70-CD27 interaction is predicted between malignant and T cells. Furthermore, coinhibitory signals mediated by TIM3 or TIGIT seem to be the main driving force for T cell exhaustion. Finally, we find that chronic hepatitis B virus infection may have a significant impact on tumor cell survival and immune evasion in DLBCL. Our results provide insights into B cell lymphomagenesis and may facilitate the design of targeted immunotherapy strategies.

Keywords: CP: Cancer; CP: Immunology; diffuse large B cell lymphoma; hepatitis B virus (HBV); immunotherapy; relapse; scRNA-seq; single-cell RNA sequencing; tumor heterogeneity; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Exome Sequencing
Hepatitis B, Chronic*
Humans
Lymphoma, Large B-Cell, Diffuse* / metabolism
Transcriptome
Tumor Microenvironment / genetics