Preclinical study of LMP1-RNAi-based anti-tumor therapy in EBV-positive nasopharyngeal carcinoma

Yuan, Qi; Chen, Bing-Hong; Huang, Dai-Jia; Zhang, Rong

doi:10.1590/1414-431x2023e12638

Cited by 1 publication

(1 citation statement)

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“…These findings are consistent with the promising efficacy of RNA interference‐based therapies in other EBV‐associated cancers. [ 45–47 ] In addition, T‐cell therapy targeting LMP1 has shown promising efficacy in EBV‐associated lymphomas, [ 48,49 ] including a recent in vivo CAR‐T investigation of NKTCL. [ 50 ]…”

Section: Discussionmentioning

confidence: 99%

Single‐Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T‐Cell Lymphoma

Li,

Luo,

Jiang

et al. 2023

Advanced Science

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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.

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Section: Discussionmentioning

confidence: 99%