Xue Huichan, Chen Yunshang, Zhou Yun
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2024 Dec 6;15:1522508. doi: 10.3389/fimmu.2024.1522508. eCollection 2024.
Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related deaths, with conventional treatments offering limited effectiveness in advanced stages, due to distant metastases and treatment resistance. Recent advancements in immunotherapy, specifically immune checkpoint inhibitors (ICIs), have shown promise, but their efficacy as standalone therapies are often insufficient. This has led to increased interest in combining ICIs with radiotherapy, known as radioimmunotherapy (iRT), to enhance treatment outcomes. This review explores the mechanisms that underlie the synergy between radiotherapy and immunotherapy. Radiotherapy can induce the "abscopal effect", eliciting systemic immune responses that reduce tumor burdens outside the treated area. It also increases the expression of major histocompatibility complex class I (MHC-I) on tumor cells, improving immune recognition. Furthermore, radiotherapy can modify the tumor microenvironment by inducing metabolic reprogramming to bolster anti-tumor immunity. We discuss strategies for optimizing iRT, including considerations of radiation doses, fractionation schedules, and treatment site selection, which significantly influence immune responses by enhancing MHC-I expression or promoting T-cell infiltration. Clinical evidence supports the efficacy of iRT in NSCLC and other cancers, though challenges in standardizing treatment protocols and managing side effects persist. Overall, radioimmunotherapy presents a promising approach to improving NSCLC treatment outcomes. Ongoing research into its mechanisms and the refinement of treatment may reshape clinical practice, offering more effective and personalized options for patients with advanced lung cancer. Further studies are essential to validate these findings and optimize therapeutic protocols.
肺癌，尤其是非小细胞肺癌（NSCLC），仍然是癌症相关死亡的主要原因，由于远处转移和治疗耐药性，传统治疗在晚期的效果有限。免疫疗法的最新进展，特别是免疫检查点抑制剂（ICIs），已显示出前景，但它们作为单一疗法的疗效往往不足。这导致人们对将ICIs与放射疗法相结合（称为放射免疫疗法，iRT）以提高治疗效果的兴趣增加。本综述探讨了放射疗法和免疫疗法协同作用的潜在机制。放射疗法可诱导“远隔效应”，引发全身免疫反应，减轻治疗区域外的肿瘤负担。它还可增加肿瘤细胞上主要组织相容性复合体I类（MHC-I）的表达，改善免疫识别。此外，放射疗法可通过诱导代谢重编程来改变肿瘤微环境，以增强抗肿瘤免疫力。我们讨论了优化iRT的策略，包括对辐射剂量、分割方案和治疗部位选择的考虑，这些因素通过增强MHC-I表达或促进T细胞浸润，对免疫反应有显著影响。临床证据支持iRT在NSCLC和其他癌症中的疗效，尽管在标准化治疗方案和管理副作用方面仍存在挑战。总体而言，放射免疫疗法为改善NSCLC治疗效果提供了一种有前景的方法。对其机制的持续研究和治疗的完善可能会重塑临床实践，为晚期肺癌患者提供更有效和个性化的选择。进一步的研究对于验证这些发现和优化治疗方案至关重要。
