Single-cell landscape of primary central nervous system diffuse large B-cell lymphoma

Nianping Liu; Chen Jiang; Xinfeng Yao; Minghao Fang; Xiaolong Qiao; Lin Zhu; Zongcheng Yang; Xuyuan Gao; Ying Ji; Chaoshi Niu; Chuandong Cheng; Kun Qu; Jun Lin

doi:10.1038/s41421-023-00559-7

Single-cell landscape of primary central nervous system diffuse large B-cell lymphoma

Cell Discov. 2023 Jun 12;9(1):55. doi: 10.1038/s41421-023-00559-7.

Authors

Nianping Liu^#¹, Chen Jiang^#^{1

2}, Xinfeng Yao^#¹, Minghao Fang³, Xiaolong Qiao⁴, Lin Zhu¹, Zongcheng Yang⁵, Xuyuan Gao¹, Ying Ji¹, Chaoshi Niu¹, Chuandong Cheng⁶, Kun Qu^{7

8

9}, Jun Lin^{10

11

12}

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
² Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, Anhui, China.
³ Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
⁴ Anhui University of Science and Technology, Huainan, Anhui, China.
⁵ Department of Stomatology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
⁶ Department of Neurosurgery, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. doctorcd@ustc.edu.cn.
⁷ Department of Neurosurgery, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. qukun@ustc.edu.cn.
⁸ Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, Anhui, China. qukun@ustc.edu.cn.
⁹ CAS Center for Excellence in Molecular Cell Sciences, The CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei, Anhui, China. qukun@ustc.edu.cn.
¹⁰ Department of Neurosurgery, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. linjun7@ustc.edu.cn.
¹¹ Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, Anhui, China. linjun7@ustc.edu.cn.
¹² CAS Center for Excellence in Molecular Cell Sciences, The CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei, Anhui, China. linjun7@ustc.edu.cn.

^# Contributed equally.

Abstract

Understanding tumor heterogeneity and immune infiltrates within the tumor-immune microenvironment (TIME) is essential for the innovation of immunotherapies. Here, combining single-cell transcriptomics and chromatin accessibility sequencing, we profile the intratumor heterogeneity of malignant cells and immune properties of the TIME in primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) patients. We demonstrate diverse malignant programs related to tumor-promoting pathways, cell cycle and B-cell immune response. By integrating data from independent systemic DLBCL and follicular lymphoma cohorts, we reveal a prosurvival program with aberrantly elevated RNA splicing activity that is uniquely associated with PCNS DLBCL. Moreover, a plasmablast-like program that recurs across PCNS/activated B-cell DLBCL predicts a worse prognosis. In addition, clonally expanded CD8 T cells in PCNS DLBCL undergo a transition from a pre-exhaustion-like state to exhaustion, and exhibit higher exhaustion signature scores than systemic DLBCL. Thus, our study sheds light on potential reasons for the poor prognosis of PCNS DLBCL patients, which will facilitate the development of targeted therapy.