放疗对肿瘤微环境的重塑及增强免疫治疗疗效机制的研究进展

以免疫检查点抑制剂(ICIs)为主的免疫治疗改变了传统癌症治疗手段,但对于大多数类型的癌症,ICIs治疗受益十分有限(10％～30％),并且在某些癌症类型中基本无效(如胰腺癌、脑胶质瘤).将ICIs治疗与现有及潜在的疗法相结合从而克服肿瘤原发性和获得性抵抗,对于提高治疗率、增加疗效的持久性和延长患者的生存期有重要意义....

New Insight on Tumor Microenvironment Remodelling and Augmented TherapeuticEfficacy of Immunotherapy by Radiotherapy

Immune checkpoint inhibitors (ICIs)-based tumor immunotherapy has changed the traditional cancer treatment. However, ICI treatment benefits small percentage of patients in most types of cancer (10%-30%), and is basically ineffective in some cancers (such as pancreatic cancer and glioma). Combining ICIs with existing and potential therapies to overcome tumor innate and acquired resistance is of great significance for improving the treatment efficacy, increasing the durability of the therapeutic effect and prolonging patients’ survival. Radiotherapy can not only kill tumor cells, but also cause the release of pro-inflammatory molecules and immune cell infiltration in tumors. In addition, radiotherapy can induce micronuclei in tumor cells, thereby activating cytosolic DNA/RNA sensors, the most important of which is the cyclic GMP-AMP synthase (cGAS)-STING pathway. Radiotherapy can also regulate immune surveillance through the expression of tumor neoantigens. In this review, we will discuss in depth the immunomodulatory effect of radiotherapy on the tumor microenvironment and its combination with ICI as a potential cancer treatment, and focus on the effects of radiotherapy on non-tumor cells in the tumor microenvironment, including dendritic cells, T cell infiltration, as well as myeloid-derived suppressor cells.