文章：

肿瘤基质来源的ANGPTL2增强免疫检查点抑制剂疗效

Tumor stroma-derived ANGPTL2 potentiates immune checkpoint inhibitor efficacy 

原文发布日期：2024-03-11 

英文摘要：

Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy has advanced rapidly in the clinic. We recently reported that tumor stroma-derived angiopoietin-like protein 2 (ANGPTL2) has tumor suppressive activity by enhancing dendritic cell-mediated CD8+ T cell anti-tumor immune responses. However, a direct impact of ANGPTL2 on ICI anti-tumor effect remains unclear. Here, we use a murine syngeneic model to show that host ANGPTL2 facilitates CD8+ T cell cross-priming and contributes to anti-tumor responses to ICIs in this context. Importantly, our analysis of public datasets indicated that ANGPTL2 expression is associated with positive responses to ICI therapy by human melanoma patients. We conclude that ANGPTL2-mediated stromal cell crosstalk facilitates anti-tumor immunity and ICI responsiveness. These findings overall provide novel insight into ANGPTL2 anti-tumor function and regulation of ICI-induced anti-tumor immunity. 

摘要翻译：

免疫检查点抑制剂（ICIs）作为癌症免疫治疗手段已在临床实践中快速发展。我们近期研究发现，肿瘤基质来源的血管生成素样蛋白2（ANGPTL2）通过增强树突状细胞介导的CD8+ T细胞抗肿瘤免疫应答，具有抑制肿瘤的活性。然而，ANGPTL2对ICI抗肿瘤效果的直接影响尚不明确。本研究通过小鼠同系移植模型证明，在此背景下，宿主ANGPTL2能促进CD8+ T细胞的交叉启动，并增强对ICIs的抗肿瘤应答。重要的是，我们对公共数据集的分析表明，ANGPTL2表达与人类黑色素瘤患者对ICI治疗的阳性反应相关。我们得出结论：ANGPTL2介导的基质细胞交互作用促进了抗肿瘤免疫和ICI反应性。这些发现为理解ANGPTL2的抗肿瘤功能及ICI诱导的抗肿瘤免疫调控机制提供了新见解。

原文链接：

Tumor stroma-derived ANGPTL2 potentiates immune checkpoint inhibitor efficacy