西湖大学发表最新Nature Immunology论文

Core Viewpoint - The study reveals the critical role of the transcription factor IRF8 in the differentiation and function of exhausted CD8⁺ T cells in cancer, highlighting its potential as a target for new immunotherapy strategies [2][3][8]. Group 1: Research Findings - The research constructed a chromatin spatial structure map of tumor-specific exhausted CD8⁺ T cells, showing that IRF8 recruits the structural protein CTCF to reshape chromatin architecture and regulate gene expression, thereby influencing the differentiation and anti-tumor functions of exhausted CD8⁺ T cells [3][6]. - During the differentiation of CD8⁺ T cells, extensive chromatin spatial structure remodeling occurs, with 45% of structures in chromatin loops being reorganized as precursor exhausted CD8⁺ T cells (Tpex) transition to terminally differentiated exhausted CD8⁺ T cells (Ttex) [6]. - The absence of IRF8 significantly impairs the differentiation of exhausted CD8⁺ T cells and their anti-tumor functions, indicating its essential role in the spatial proximity reorganization between enhancers and promoters of genes related to T cell exhaustion [6][8]. Group 2: Implications for Immunotherapy - The findings suggest that IRF8-dependent chromatin topology plays a crucial role in the differentiation of exhausted CD8⁺ T cells, providing a potential target for developing new cancer immunotherapy strategies aimed at enhancing CD8⁺ T cell activity and improving anti-tumor immune responses [8].