Abstract
"Epstein-Barr virus (EBV) is the oncogenic driver of multiple cancers. However, the underlying mechanism of virus-cancer immunological interaction during disease pathogenesis remains largely elusive. Here we reported the first comprehensive proteogenomic characterization of natural killer/T-cell lymphoma (NKTCL), a representative disease model to study EBV-induced lymphomagenesis, incorporating genomic, transcriptomic, and in-depth proteomic data. Our multi-omics analysis of NKTCL revealed that EBV gene pattern correlated with immune-related oncogenic signaling. Single-cell transcriptome further delineated the tumor microenvironment as immune-inflamed, -deficient, and -desert phenotypes, in association with different setpoints of cancer-immunity cycle. EBV interacted with transcriptional factors to provoke GPCR interactome (GPCRome) reprogramming. Enhanced expression of chemokine receptor-1 (CCR1) on malignant and immunosuppressive cells modulated virus-cancer interaction on microenvironment. Therapeutic targeting CCR1 showed promising efficacy with EBV eradication, T-cell activation, and lymphoma cell killing in NKTCL organoid. Collectively, our study identified a previously unknown GPCR-mediated malignant progression and translated sensors of viral molecules into EBV-specific anti-cancer therapeutics."
Authors
Jie Xiong, Yu-Ting Dai, Wen-Fang Wang, Hao Zhang, Chao-Fu Wang, Tong Yin, Shu Cheng, Hui-Juan Zhong, Shan-He Yu, Lu Jiang, Sheng-Yue Wang, Hai Fang, Rui-Hong Zhang, Yue Zhu, Hong-Mei Yi, Xu-Feng Jiang, Jia-Yi Chen, Li Wang, Peng-Peng Xu, Sai-Juan Chen, Wei-Li Zhao
Tags
CCR1, Epstein-Barr virus, Lymphoma, Microenvironment, Multi-omics, Single-cell transcriptome