1. Single‐Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T‐Cell Lymphoma
- Author
-
Yi‐Qi Li, Chun‐Ling Luo, Jia‐Xin Jiang, Shuai He, Yang Liu, Wen‐Xin Yan, Yi Xia, Qian Cui, Ying Huang, Jing Quan Lim, Dachuan Huang, Izzah Nabilah Hussein, Yan Gao, Guo‐Wang Lin, Yi‐Hong Ling, Dong Ma, Yue‐Tong Zhang, Jason Yongsheng Chan, Pan‐Pan Wei, Xiao‐Xiao Wang, Chee Leong Cheng, Jie Xiong, Wei‐Li Zhao, Choon Kiat Ong, Soon Thye Lim, Hui‐Qiang Huang, Rou‐Jun Peng, and Jin‐Xin Bei
- Subjects
DPP4 ,immunosuppression ,LMP1+ malignant NK cells ,NKTCL ,scRNA‐seq ,Science - Abstract
Abstract Extranodal natural killer/T‐cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein–Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single‐cell RNA sequencing (scRNA‐seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single‐cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV‐encoded genes and low infiltration of tumor‐associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single‐cell resolution, highlighting the crucial role of malignant NK cells with EBV‐encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.
- Published
- 2023
- Full Text
- View/download PDF