Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China.
Department of Hematology and Medical Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
Biomed Pharmacother. 2021 Jul;139:111607. doi: 10.1016/j.biopha.2021.111607. Epub 2021 May 6.
Leakage and compression of blood vessels may result in deprivation of blood flow to a large number of tumor tissues, which can lead to tumor hypoxia. Hypoxia induces an increase in the expression of hypoxia-inducible factor 1 in tumor cells, which induces angiogenesis in tumors through the high expression of vascular endothelial growth factor, thereby forming a positive feedback vicious circle. Improving hypoxia by normalizing blood vessels and improving radiosensitivity by immunotherapy has emerged as a new application of combined immunotherapy and radiotherapy. Interferon γ produced by CD4 + /CD8 + T cells, induced by immune checkpoint inhibitors, plays an important role in the normalization of blood vessels; tumor-associated eosinophils also play a role in the process of immunotherapy-induced blood vessel normalization. In addition, the reduction in regulatory T cells induced by immune checkpoint inhibitors can increase eosinophil levels, which promotes the further development of vascular normalization mechanisms. This review focuses on the mechanism of immunotherapy to normalize blood vessels, and proposes a good prospect for improving hypoxia. Due to the narrow vascular normalization window of anti-angiogenesis therapy, discovery of the vascular normalization effect of immunotherapy provides a new idea for the combined application of immunotherapy and radiotherapy. The enlarged vascular normalization window and improved hypoxia provide a good opportunity for the subsequent implementation of radiotherapy. The above sorting and analysis may pave the way for a promising strategy for cancer treatment via combined immunotherapy and radiotherapy.
血管渗漏和压缩可能导致大量肿瘤组织血液供应中断，进而导致肿瘤缺氧。缺氧会诱导肿瘤细胞中缺氧诱导因子 1 的表达增加，通过血管内皮生长因子的高表达诱导肿瘤血管生成，从而形成正反馈恶性循环。通过使血管正常化来改善缺氧，以及通过免疫疗法提高放射敏感性，已成为联合免疫疗法和放射疗法的新应用。免疫检查点抑制剂诱导的 CD4+/CD8+T 细胞产生的干扰素 γ 在血管正常化中发挥重要作用；肿瘤相关嗜酸性粒细胞也在免疫治疗诱导的血管正常化过程中发挥作用。此外，免疫检查点抑制剂诱导的调节性 T 细胞减少可增加嗜酸性粒细胞水平，从而促进血管正常化机制的进一步发展。本文综述了免疫疗法使血管正常化的机制，并提出了改善缺氧的良好前景。由于抗血管生成治疗的血管正常化窗口较窄，免疫疗法的血管正常化作用的发现为免疫疗法和放射疗法的联合应用提供了新的思路。扩大的血管正常化窗口和改善的缺氧为随后实施放射治疗提供了良好的机会。上述分类和分析可能为联合免疫疗法和放射疗法治疗癌症开辟了一条有希望的策略。
