1. Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma
- Author
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Junshang Ge, Yi Meng, Jiayue Guo, Pan Chen, Jie Wang, Lei Shi, Dan Wang, Hongke Qu, Pan Wu, Chunmei Fan, Shanshan Zhang, Qianjin Liao, Ming Zhou, Bo Xiang, Fuyan Wang, Ming Tan, Zhaojian Gong, Wei Xiong, and Zhaoyang Zeng
- Subjects
Science - Abstract
Abstract Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8+ T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in vivo experiments demonstrate that circE7 suppresses the function and activity of T cells by downregulating the transcription of LGALS9, which encodes the galectin-9 protein. The molecular mechanism involves circE7 binding to acetyl-CoA carboxylase 1 (ACC1), promoting its dephosphorylation and thereby activating ACC1. Activated ACC1 reduces H3K27 acetylation at the LGALS9 gene promoter, leading to decreased galectin-9 expression. Notably, galectin-9 interacts with immune checkpoint molecules TIM-3 and PD-1, inhibiting the secretion of cytotoxic cytokines by T cells and promoting T cell apoptosis. Here, we demonstrate a mechanism by which HPV promotes immune evasion in HNSCC through a circE7-driven epigenetic modification and propose a potential immunotherapy strategy for HNSCC that involves the combined use of anti-PD-1 and anti-TIM-3 inhibitors.
- Published
- 2024
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