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.
实体肿瘤中的异常血管系统导致血液灌注不良、缺氧、低pH值及免疫逃逸现象，同时塑造了肿瘤微环境并影响免疫治疗的反应。抗血管生成治疗与免疫治疗的联合应用已成为一种前景广阔的策略，旨在实现血管正常化并充分释放免疫治疗的潜力。然而，肿瘤特异性缺氧微环境引发的血管生成与免疫抑制机制具有不可预测性和冗余性，这表明此类联合疗法仍需进一步评估以改善患者预后。本文系统综述了肿瘤血管生成与免疫调节之间的相互作用，重点探讨了YY1-HIF轴调控肿瘤血管及免疫微环境的功能与机制。此外，我们讨论了靶向YY1及其他策略（如纳米载体递送系统、工程化免疫细胞CAR-T）在实现肿瘤血管正常化、重建免疫许可微环境以提升癌症治疗效果方面的潜在价值。
Clinical Potential of YY1-Hypoxia Axis for Vascular Normalization and to Improve Immunotherapy
肿瘤(癌症)患者之家