环状RNA（circRNA）已被证明在肿瘤发展和肿瘤免疫学中发挥重要作用。然而，circRNA的全基因组特征及其在胆囊癌（GBC）免疫学和免疫治疗中的作用一直缺乏。我们对 GBC 中的 circRNA 景观进行了全面的表征，揭示了 GBC 特异性的 circRNA。我们的分析发现，circRNA 在细胞增殖中显着富集，并参与癌症相关标志。特别是，circAATF在GBC中表达上调，与AATF mRNA表达呈正相关，并促进GBC细胞生长。通过整合计算和实验方法，我们发现 circAATF 与 CD4 T 细胞丰度和 PD-L1 水平呈正相关，并增强了 GBC 抗 PD-L1 免疫治疗的临床益处。我们进一步证明，circAATF 通过激活磷酸化 AKT 并充当 miR-142-5p 的海绵来提高 PD-L1 水平。 CircAATF 与 CD4 T 细胞和 PD-L1 水平呈正相关，并显示出辅助 GBC 抗 PD-L1 免疫治疗的潜力。我们的研究深入了解了 circAATF 在 GBC 肿瘤发展和免疫学中的作用，并加速 GBC 免疫治疗策略的开发。亮点：我们对胆囊癌 (GBC) 中的 circRNA 景观进行了全面的表征。 CircAATF 与 CD4 T 细胞丰度和 PD-L1 表达呈正相关，并显示可促进小鼠模型中的 PD-L1 治疗。 CircAATF 可以通过磷酸化 AKT 和线性 AATF 提高 PD-L1 水平，后者通过充当 miR-142-5p 的海绵来上调 PD-L1。© 2024 作者。约翰·威利出版的《临床与转化医学》

Circular RNAs (circRNAs) have been shown to play important roles in tumour development and tumour immunology. However, genome-wide characterisation of circRNAs and their roles in the immunology and immunotherapy of gallbladder carcinoma (GBC) has been lacking. We present a comprehensive characterisation of the circRNA landscape in GBC, revealing GBC-specific circRNAs. Our analysis found that circRNAs are significantly enriched in cell proliferation and are involved in cancer-related hallmarks. In particular, circAATF was upregulated in GBC, which was positively correlated with AATF mRNA expression, and promoted GBC cell growth. Through integrating computational and experimental approaches, we revealed that circAATF is positively associated with the CD4+ T cell abundance and PD-L1 level, and enhances the clinical benefits of anti-PD-L1 immunotherapy for GBC. We further demonstrate that circAATF elevates the PD-L1 level by activating phosphorylated AKT and acting as a sponge for miR-142-5p. CircAATF is positively associated with CD4+ T cells and PD-L1 levels and shows potential to aid anti-PD-L1 immunotherapy for GBC. Our study provides insights into roles of circAATF in the tumour development and immunology of GBC and accelerates the development of therapeutic strategies for GBC immunotherapy. HIGHLIGHTS: We present a comprehensive characterisation of circRNA landscape in gallbladder carcinoma (GBC). CircAATF is positively associated with CD4+ T cell abundance and PD-L1 expression and is shown to promote PD-L1 treatment in mouse model. CircAATF can elevate PD-L1 level through phosphorylated AKT and linear AATF, which upregulates PD-L1 by acting as a sponge of miR-142-5p.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.