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.

使用免疫检查点抑制剂（ICIs）作为癌症免疫疗法在临床上进展迅速。我们最近报道，肿瘤基质衍生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细胞抗肿瘤免疫反应而具有肿瘤抑制活性。然而，ANGPTL2对ICI抗肿瘤效果的直接影响仍不清楚。在这里，我们使用小鼠同基因模型来证明宿主 ANGPTL2 促进 CD8 ⁺ T 细胞交叉启动，并有助于在此背景下对 ICI 的抗肿瘤反应。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 介导的基质细胞串扰促进抗肿瘤免疫和 ICI 反应。这些发现总体上为 ANGPTL2 抗肿瘤功能和 ICI 诱导的抗肿瘤免疫调节提供了新的见解。