Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma

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 ()
Additional contact information
Junshang Ge: Central South University
Yi Meng: Central South University
Jiayue Guo: Central South University
Pan Chen: Central South University
Jie Wang: Central South University
Lei Shi: Central South University
Dan Wang: Central South University
Hongke Qu: Central South University
Pan Wu: Central South University
Chunmei Fan: Central South University
Shanshan Zhang: Central South University
Qianjin Liao: Central South University
Ming Zhou: Central South University
Bo Xiang: Central South University
Fuyan Wang: Central South University
Ming Tan: China Medical University
Zhaojian Gong: Central South University
Wei Xiong: Central South University
Zhaoyang Zeng: Central South University

Nature Communications, 2024, vol. 15, issue 1, 1-18

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.

Date: 2024
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DOI: 10.1038/s41467-024-52981-4

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