The tumor-associated vasculature imposes major structural and biochemical barriers to the infiltration of effector T cells and effective tumor control. Correlations between stimulator of interferon genes (STING) pathway activation and spontaneous T cell infiltration in human cancers led us to evaluate the effect of STING-activating nanoparticles (STANs), which are a polymersome-based platform for the delivery of a cyclic dinucleotide STING agonist, on the tumor vasculature and attendant effects on T cell infiltration and antitumor function. In multiple mouse tumor models, intravenous administration of STANs promoted vascular normalization, evidenced by improved vascular integrity, reduced tumor hypoxia, and increased endothelial cell expression of T cell adhesion molecules. STAN-mediated vascular reprogramming enhanced the infiltration, proliferation, and function of antitumor T cells and potentiated the response to immune checkpoint inhibitors and adoptive T cell therapy. We present STANs as a multimodal platform that activates and normalizes the tumor microenvironment to enhance T cell infiltration and function and augments responses to immunotherapy.

中文翻译：

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STING 激活纳米粒子使血管-免疫界面正常化，以增强癌症免疫治疗


肿瘤相关脉管系统对效应 T 细胞的浸润和有效的肿瘤控制施加了主要的结构和生化障碍。人类癌症中干扰素基因刺激剂 (STING) 通路激活与自发 T 细胞浸润之间的相关性使我们评估了 STING 激活纳米颗粒 (STAN) 的效果，STAN 是一种基于聚合物囊泡的平台，用于递送环状二核苷酸 STING 激动剂，对肿瘤血管系统以及对 T 细胞浸润和抗肿瘤功能的伴随影响。在多种小鼠肿瘤模型中，静脉注射 STAN 可以促进血管正常化，改善血管完整性、减少肿瘤缺氧以及增加内皮细胞 T 细胞粘附分子的表达。 STAN 介导的血管重编程增强了抗肿瘤 T 细胞的浸润、增殖和功能，并增强了对免疫检查点抑制剂和过继性 T 细胞治疗的反应。我们将 STAN 作为一个多模式平台，可以激活肿瘤微环境并使其正常化，从而增强 T 细胞浸润和功能，并增强对免疫治疗的反应。