文章：

通过靶向肿瘤纤维化基质与血管生成调节肿瘤免疫以治疗肺癌

Modulating Tumor Immunity by Targeting Tumor Fibrotic Stroma and Angiogenic Vessels for Lung Cancer Treatment

原文发布日期：8 July 2024

DOI: 10.3390/cancers16132483

类型: Article

开放获取: 是

英文摘要：

Fibrotic stroma and angiogenic tumor vessels play an important role in modulating tumor immunity. We previously reported a rationally designed protein (ProAgio) that targets integrin αvβ3at a novel site. ProAgio induces the apoptosis of cells that express high levels of the integrin. Both activated cancer-associated fibroblasts (CAFs) and angiogenic endothelial cells (aECs) in tumors express high levels of integrin αvβ3. ProAgio simultaneously and specifically induces apoptosis in CAFs and aECs in tumors. We provide evidence here that the depletion of CAFs and the elimination of leaky tumor angiogenic vessels by ProAgio alter tumor immunity. ProAgio reduces CD4+Treg and Myeloid-derived suppressor cells (MDSCs), increases CD8+T-cells, and increases the M1/M2 macrophage ratio in the tumor. The depletion of dense fibrotic stroma (CAFs) by ProAgio decreases theProgrammed Death Ligand 1(PDL-1) levels in the stroma areas surrounding the tumors, and thus strongly increases the delivery of anti-PDL-1 antibody to the target cancer cells. The impact of ProAgio on tumor immunity provides strong synergistical effects of checkpoint inhibitors on lung cancer treatment.

摘要翻译： 

纤维化基质与血管生成性肿瘤血管在调节肿瘤免疫中扮演着重要角色。我们先前报道了一种理性设计的蛋白质（ProAgio），其靶向整合素αvβ3的一个新型位点。ProAgio能够诱导高表达该整合素的细胞发生凋亡。肿瘤中活化的癌症相关成纤维细胞（CAFs）与血管生成性内皮细胞（aECs）均高表达整合素αvβ3。ProAgio可同时特异性诱导肿瘤内CAFs与aECs的凋亡。本文提供的证据表明，ProAgio通过清除CAFs及消除渗漏性肿瘤血管生成性血管，从而改变肿瘤免疫状态。ProAgio能减少肿瘤中CD4+调节性T细胞（Treg）与髓源性抑制细胞（MDSCs），增加CD8+T细胞，并提高M1/M2巨噬细胞比例。ProAgio对致密纤维化基质（CAFs）的清除降低了肿瘤周围基质区域中程序性死亡配体1（PDL-1）的水平，从而显著增强抗PDL-1抗体向靶癌细胞的递送效率。ProAgio对肿瘤免疫的影响为检查点抑制剂在肺癌治疗中提供了强大的协同增效作用。

原文链接：

Modulating Tumor Immunity by Targeting Tumor Fibrotic Stroma and Angiogenic Vessels for Lung Cancer Treatment