肝癌免疫治疗联合放射治疗进展

Advances in immunotherapy combined with radiotherapy for hepatocellular carcinoma

免疫检查点抑制剂(ICI)的应用给肝细胞癌(HCC)的全身性治疗带来了新的选择。肿瘤的治疗经历了从传统治疗模式向靶向肿瘤微环境(TME)模式的巨大转变。然而,单独使用免疫检查点阻断(ICB)药物治疗的疗效有限,而将免疫疗法与当前的治疗策略相结合可能产生更好的效果。放射治疗(RT)是包括HCC在内的实体癌症治疗中不可或缺的组成部分。体部立体定向放射治疗(SBRT)在过去的10年中已被用于治疗原发性HCC并且取得了不错的成绩。大剂量的放疗更容易产生远位效应,提示其潜在的免疫激活作用。免疫治疗与放射治疗相结合可能是一种有希望协同增强疗效的策略。其机制可能是射线照射到肿瘤部位会同时影响肿瘤细胞和周围的基质细胞。辐射诱导的癌细胞损伤暴露了肿瘤特异性抗原,使其在免疫监视中可见,并促进细胞毒性T细胞的启动和激活。RT和ICB联合治疗疗效在一些临床研究中也得到了证实。但是要最大程度地发挥两者联用的疗效是有待解决的挑战。文章总结了HCC中RT和ICB联合治疗的进展,以及放疗和免疫系统协同作用的机制,并讨论了目前放疗和免疫检查点阻断疗法中的挑战以及未来增强这种组合可能的方法。

The application of immune checkpoint inhibitors(ICB)has led to significant advances in systemic therapy for advanced hepatocellular carcinoma(HCC).The systemic treatment of cancer has experienced tremendous paradigm towards targeting tumor microenvironment(TME).However,the efficacy of ICB therapy alone is limited,and combining immunotherapy with current treatment strategies may yield better results.Radiotherapy(RT)is an integral part of solid cancer therapy including HCC.Stereotactic body radiotherapy(SBRT)has been used to treat primary HCC for the past ten years and has achieved good results.High dose radiotherapy is more likely to produce abscopal effects,suggesting its potential role in immune activation.The combination of immunotherapy and radiotherapy may be a promising strategy for synergistically enhancing efficacy.Radiation induced cancer cell damage exposes tumor-specific antigens that are visible under immune surveillance and promotes the initiation and activation of cytotoxic T cells.Radiation induced tumor microenvironmental regulation may also promote the recruitment and infiltration of immune cells.The efficacy of RT combined with ICB has also been demonstrated in some clinical studies.But there are still unsolved challenges to make the most appropriate combination strategy.Here,we summarize the advances in combination therapy of RT and ICB in HCC,the mechanisms by which radiotherapy and the immune system work together,and discuss the challenges of current radiotherapy and immune checkpoint blocking therapies and possible strategies to enhance this combination in the future.