其中最为严重的恶性肿瘤之一是三阴性乳腺癌(TNBC)。其以临床上快速进展为特征。环状RNA(circRNA)在几乎所有癌症中异常表达，并在肿瘤免疫逃逸中发挥重要作用。然而，环状成纤维细胞生长因子受体4 RNA（circFGFR4）在TNBC中的生物学作用尚不清楚。使用定量实时聚合酶链反应(qRT-PCR)检测了TNBC组织和非肿瘤组织中circFGFR4的表达。通过分析临床组织评估了circFGFR4在TNBC免疫逃逸中的作用。通过体内circRNA沉淀、RNA免疫沉淀和荧光素酶报告基因试验，探索了circFGFR4和miR-185-5p之间的相互作用。我们的结果表明，circFGFR4在TNBC组织中明显上调。上调的circFGFR4表达与肿瘤组织中CD8+T细胞浸润减少、对抗程序性细胞死亡蛋白1（PD-1）免疫治疗的耐药性以及TNBC患者和携带TNBC肿瘤的小鼠有关。强制表达circFGFR4抑制了携带TNCB肿瘤的小鼠组织切片中的CD8+T细胞浸润。从机制上讲，circFGFR4竞争性地吸附miR-185-5p，并防止miR-185-5p降低C-X-C模体趋化因子受体4（CXCR4）水平。最终，我们的结果表明，circFGFR4通过调节miR-185-5p/CXCR4轴在TNBC中发挥了免疫逃逸和抗PD-1免疫治疗耐药性的重要作用，因此表明circFGFR4在预测对抗PD-1免疫治疗的敏感性和作为TNBC的免疫治疗靶点具有显著潜力。 © 2023 Wang等。

One of the most catastrophic malignant tumors is triple negative breast cancer (TNBC). It is characterized by rapid progression in the clinic. CircRNAs are abnormally expressed in almost all cancers and play important roles in tumor immune evasion. Nevertheless, the biological roles of the circular fibroblast growth factor receptor 4 RNA (circFGFR4) in TNBC remain unclear.The expression of circFGFR4 in TNBC tissues and paired nontumor tissues was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The role of circFGFR4 in TNBC immune evasion was estimated by analyzing clinical tissues. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore interaction between circFGFR4 and miR-185-5p.Our results indicated that circFGFR4 was significantly overexpressed in TNBC tissues. Upregulated circFGFR4 expression was correlated with decreased CD8+ T cell infiltration in tumor tissues and resistance to anti-programmed cell death 1 (PD-1) immunotherapy in TNBC patients and mice bearing TNBC tumors. Forced circFGFR4 expression inhibited CD8+ T cell infiltration in tissue sections from TNCB tumor bearing mice. Mechanistically, circFGFR4 competitively sponged miR-185-5p and prevented miR-185-5p from decreasing the levels of C-X-C motif chemokine receptor 4 (CXCR4).Ultimately, our results indicated that circFGFR4 plays an important role in immune evasion and anti-PD-1 immunotherapy resistance via regulates miR-185-5p/CXCR4 axis in TNBC, thus suggesting that circFGFR4 has significant potential as a biomarker for predicting sensitivity to anti-PD-1 immunotherapy and as an immunotherapeutic target for TNBC.© 2023 Wang et al.