Department of Radiation Oncology, Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Clin Exp Immunol. 2024 Oct 16;218(2):188-198. doi: 10.1093/cei/uxae075.
Preclinical data suggest that type I interferon (IFN) responsiveness is essential for the antitumor effects of radiotherapy (RT). However, its clinical value remains unclear. This study aimed to explore this from a clinical perspective. In cohort 1, data from 152 hepatocellular carcinoma (HCC) patients who received RT were analyzed. Blood samples were taken 1 day before and 2 weeks after RT. RT was found to increase serum levels of IFN-β (a subtype of IFN-I) in HCC patients (3.42 ± 1.57 to 5.51 ± 2.11 pg/ml, P < 0.01), particularly in those with favorable responses. Higher post-RT serum IFN-β levels (≥4.77 pg/ml) were associated with better progression-free survival (HR = 0.58, P < 0.01). Cohort 2 included 46 HCC patients, including 23 who underwent preoperative RT and 23 matched control HCC who received surgical resection without RT. Formalin-fixed paraffin-embedded samples were obtained. Neoadjuvant RT significantly increased IFN-β expression in tumor tissues compared to direct surgery (8.13% ± 5.19% to 15.10% ± 5.89%, P < 0.01). Higher post-RT IFN-β (>median) indicated better disease-free survival (P = 0.049). Additionally, increased CD11c+MHCII+CD141+ antigen-presenting cell subsets and CD103+CD39+CD8+ tumor-infiltrating lymphocytes were found in the higher IFN-β group (P = 0.02, P = 0.03), which may contribute to the favorable prognosis in higher IFN-β group. Collectively, these findings suggest that IFN-β response activated by radiation may serve as a prognostic biomarker for HCC patients undergoing RT.
临床前数据表明，I 型干扰素（IFN）反应对于放射治疗（RT）的抗肿瘤作用至关重要。然而，其临床价值仍不清楚。本研究旨在从临床角度探讨这一问题。在队列 1 中，分析了 152 例接受 RT 的肝细胞癌（HCC）患者的数据。在 RT 前 1 天和 RT 后 2 周采集血样。结果发现，RT 增加了 HCC 患者血清中 IFN-β（IFN-I 的一种亚型）的水平（3.42±1.57 至 5.51±2.11 pg/ml，P<0.01），特别是在反应良好的患者中。较高的 RT 后血清 IFN-β水平（≥4.77 pg/ml）与更好的无进展生存期相关（HR=0.58，P<0.01）。队列 2 包括 46 例 HCC 患者，其中 23 例接受术前 RT，23 例匹配的 HCC 患者接受无 RT 的手术切除。获得福尔马林固定石蜡包埋样本。与直接手术相比，新辅助 RT 显著增加了肿瘤组织中的 IFN-β 表达（8.13%±5.19%至 15.10%±5.89%，P<0.01）。较高的 RT 后 IFN-β（>中位数）提示无疾病生存更好（P=0.049）。此外，在 IFN-β 较高组中发现了更多的 CD11c+MHCII+CD141+抗原呈递细胞亚群和 CD103+CD39+CD8+肿瘤浸润淋巴细胞（P=0.02，P=0.03），这可能有助于 IFN-β 较高组的良好预后。总之，这些发现表明，辐射激活的 IFN-β 反应可能成为接受 RT 的 HCC 患者的预后生物标志物。
