Zhou Yong, Liu Zhengcheng, Yu Ao, Zhao Gefei, Chen Baojun
Department of Thoracic Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, People's Republic of China.
Immunotargets Ther. 2024 Dec 31;13:813-829. doi: 10.2147/ITT.S494670. eCollection 2024.
In recent years, the combination of immune checkpoint inhibitors (ICIs) with antiangiogenic agents has led to significant breakthroughs in cancer treatment. Such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Antiangiogenic therapy plays a pivotal role in normalizing blood vessels and remodeling the tumor immune microenvironment while ICIs not only enhance the host's antitumor immune response by blocking negative regulatory signals but also promote vascular normalization. The communication between the vasculature and immune system enables the combined use of ICIs and antiangiogenic therapy to have a synergistic effect. Clinical research has also demonstrated that this combination therapy can significantly improve the efficacy and survival of patients with various solid tumors, the addition of pembrolizumab to axitinib can significantly improve PFS (15.4 m vs 11.1 m) compared to sunitinib in first-line treatments of advanced renal cell carcinoma (RCC). Bevacizumab is the first approved anti-VEGF monoclonal antibody. Bevacizumab in combination with atezolizumab obtain significant benefit in terms of PFS (6.9 m vs 4.3 m) compared to sorafenib in advanced hepatocellular carcinoma (HCC). In addition, a series of investigations have been conducted in other solid tumors, such as colorectal cancer (CRC). Future research directions include the development of novel antiangiogenic agents and ICIs, the exploration of other combination strategies (eg, with chemotherapy or targeted therapy), and the identification of biomarkers for patient selection and monitoring response to therapy. Additionally, more studies are needed to understand the optimal timing and sequencing of these therapies to maximize patient benefit. This review aims to elucidate the mechanisms of action of ICIs plus antiangiogenic drugs and provide summaries of related clinical trials. Meanwhile, we outline the current challenges faced and future directions, include the identification of biomarkers for patient selection and monitoring response to therapy, particularly highlighting the newer therapy strategies.
近年来,免疫检查点抑制剂(ICI)与抗血管生成药物的联合应用在癌症治疗方面取得了重大突破。例如程序性细胞死亡蛋白1(PD-1)、程序性细胞死亡配体1(PD-L1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)。抗血管生成疗法在使血管正常化和重塑肿瘤免疫微环境方面发挥着关键作用,而ICI不仅通过阻断负性调节信号增强宿主的抗肿瘤免疫反应,还能促进血管正常化。脉管系统与免疫系统之间的相互作用使得ICI与抗血管生成疗法联合使用具有协同效应。临床研究也表明,这种联合疗法可显著提高各种实体瘤患者的疗效和生存率,在晚期肾细胞癌(RCC)的一线治疗中,与舒尼替尼相比,帕博利珠单抗联合阿昔替尼可显著改善无进展生存期(PFS)(15.4个月对11.1个月)。贝伐单抗是首个获批的抗VEGF单克隆抗体。在晚期肝细胞癌(HCC)中,与索拉非尼相比,贝伐单抗联合阿特珠单抗在PFS方面获得显著益处(6.9个月对4.3个月)。此外,还在其他实体瘤如结直肠癌(CRC)中进行了一系列研究。未来的研究方向包括开发新型抗血管生成药物和ICI、探索其他联合策略(如与化疗或靶向治疗联合)以及确定用于患者选择和监测治疗反应的生物标志物。此外,还需要更多研究来了解这些疗法的最佳时机和顺序,以最大程度地使患者受益。本综述旨在阐明ICI联合抗血管生成药物的作用机制,并提供相关临床试验的总结。同时,我们概述了当前面临的挑战和未来方向,包括确定用于患者选择和监测治疗反应的生物标志物,特别强调了更新的治疗策略。