Meo Concetta, de Nigris Filomena
Department of Precision Medicine, School of Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Cancers (Basel). 2024 Jan 23;16(3):491. doi: 10.3390/cancers16030491.
Abnormal vasculature in solid tumors causes poor blood perfusion, hypoxia, low pH, and immune evasion. It also shapes the tumor microenvironment and affects response to immunotherapy. The combination of antiangiogenic therapy and immunotherapy has emerged as a promising approach to normalize vasculature and unlock the full potential of immunotherapy. However, the unpredictable and redundant mechanisms of vascularization and immune suppression triggered by tumor-specific hypoxic microenvironments indicate that such combination therapies need to be further evaluated to improve patient outcomes. Here, we provide an overview of the interplay between tumor angiogenesis and immune modulation and review the function and mechanism of the YY1-HIF axis that regulates the vascular and immune tumor microenvironment. Furthermore, we discuss the potential of targeting YY1 and other strategies, such as nanocarrier delivery systems and engineered immune cells (CAR-T), to normalize tumor vascularization and re-establish an immune-permissive microenvironment to enhance the efficacy of cancer therapy.
实体瘤中的异常血管系统会导致血液灌注不良、缺氧、低pH值和免疫逃逸。它还塑造了肿瘤微环境并影响免疫治疗的反应。抗血管生成疗法和免疫疗法的联合已成为一种有前景的方法，可使血管系统正常化并释放免疫疗法的全部潜力。然而，肿瘤特异性缺氧微环境引发的血管生成和免疫抑制的不可预测和冗余机制表明，此类联合疗法需要进一步评估以改善患者预后。在此，我们概述了肿瘤血管生成与免疫调节之间的相互作用，并综述了调节血管和免疫肿瘤微环境的YY1-HIF轴的功能和机制。此外，我们讨论了靶向YY1的潜力以及其他策略，如纳米载体递送系统和工程免疫细胞（CAR-T），以使肿瘤血管生成正常化并重新建立免疫许可微环境，从而提高癌症治疗的疗效。
