抗血管生成治疗是对抗免疫抑制肿瘤微环境（TME）和提高抗肿瘤免疫力的公认方法。 PB101 是一种糖基化诱饵受体，基于 VEGFR1 主链，以高亲和力与 VEGF-A 和 PlGF 结合。在此，我们阐明了 PB101 诱导的肿瘤血管生成和免疫重塑，从而增强抗 PD-L1 免疫检查点阻断。 PB101 通过抑制血管生成和增强 CD8 T 细胞浸润到肿瘤中来抑制肿瘤生长。 PB101 诱导抗肿瘤免疫的强大重编程并激活瘤内 CD8 T 细胞。 PB101的抗肿瘤功效主要依赖于CD8 T细胞和IFN-γ。 PB101 以不同于传统 VEGF 诱饵受体 VEGF 陷阱的方式重新编程肿瘤免疫。凭借其强大的免疫调节能力，PB101 与抗 PD-L1 协同作用，引发增强的抗肿瘤免疫力。 PB101和抗PD-L1的结合可以建立针对肿瘤复发和转移的持久保护性免疫。这项研究的结果为 PB101 的进一步临床开发提供了科学依据，特别是与免疫检查点抑制剂联合使用时，作为晚期癌症的潜在治疗方法。© 2023 作者。经泰勒许可出版

Antiangiogenic therapy is a recognized method for countering the immunosuppressive tumor microenvironment (TME) and improving anti-tumor immunity. PB101 is a glycosylated decoy receptor that binds to VEGF-A and PlGF with high affinity, based on the VEGFR1 backbone. Here, we elucidated PB101-induced remodeling of tumor angiogenesis and immunity, which enhances anti-PD-L1 immune checkpoint blockade. PB101 inhibited tumor growth by suppressing angiogenesis and enhancing CD8+ T cell infiltration into the tumors. PB101 induced robust reprogramming of antitumor immunity and activates intratumoral CD8+ T cells. Anti-tumor efficacy of PB101 is mostly dependent on CD8+ T cells and IFN-γ. PB101 reprograms tumor immunity in a manner distinct from that of the conventional VEGF decoy receptor, VEGF-trap. With its potent immune-modulating capability, PB101 synergizes with an anti-PD-L1, triggering strengthened antitumor immunity. Combining PB101 and anti-PD-L1 could establish durable protective immunity against tumor recurrence and metastasis. The findings of this study offer scientific rationales for further clinical development of PB101, particularly when used in combination with immune checkpoint inhibitors, as a potential treatment for advanced cancers.© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.