Department of Biomedical Engineering and of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Cells. 2023 May 3;12(9):1305. doi: 10.3390/cells12091305.
The purpose of this study was to develop a cell-cell interaction model that could predict a tumor's response to radiotherapy (RT) combined with CTLA-4 immune checkpoint inhibition (ICI) in patients with hepatocellular carcinoma (HCC). The previously developed model was extended by adding a new term representing tremelimumab, an inhibitor of CTLA-4. The distribution of the new immune activation term was derived from the results of a clinical trial for tremelimumab monotherapy (NCT01008358). The proposed model successfully reproduced longitudinal tumor diameter changes in HCC patients treated with tremelimumab (complete response = 0%, partial response = 17.6%, stable disease = 58.8%, and progressive disease = 23.6%). For the non-irradiated tumor control group, adding ICI to RT increased the clinical benefit rate from 8% to 32%. The simulation predicts that it is beneficial to start CTLA-4 blockade before RT in terms of treatment sequences. We developed a mathematical model that can predict the response of patients to the combined CTLA-4 blockade with radiation therapy. We anticipate that the developed model will be helpful for designing clinical trials with the ultimate aim of maximizing the efficacy of ICI-RT combination therapy.
本研究旨在开发一种细胞间相互作用模型，以预测肝癌 (HCC) 患者接受放射治疗 (RT) 联合 CTLA-4 免疫检查点抑制 (ICI) 治疗的反应。该模型通过添加一个新术语来扩展先前开发的模型，该术语代表 CTLA-4 抑制剂 tremelimumab。新免疫激活项的分布源自 tremelimumab 单药治疗的临床试验结果 (NCT01008358)。所提出的模型成功地复制了接受 tremelimumab 治疗的 HCC 患者的纵向肿瘤直径变化（完全缓解 = 0%，部分缓解 = 17.6%，稳定疾病 = 58.8%，进展性疾病 = 23.6%）。对于未照射的肿瘤对照组，将 ICI 加入 RT 后，临床获益率从 8%增加到 32%。模拟预测，从治疗顺序的角度来看，在 RT 之前开始 CTLA-4 阻断是有益的。我们开发了一种可以预测患者对联合 CTLA-4 阻断与放射治疗反应的数学模型。我们预计，开发的模型将有助于设计临床试验，最终目的是最大限度地提高 ICI-RT 联合治疗的疗效。
