Systemic antitumor responses to hypofractionated radiotherapy plus Poly(I:C) in advanced hepatocellular carcinoma: A phase 2 trial.

IF 13.3 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2026-10-20 DOI:10.1016/j.medj.2026.101331

Liman Qiu, Qizhen Huang, Xinting Pan, Geng Chen, Wenhui Liu, Kai Wang, Yang Zhou, Rong Xie, Xiuqing Dong, Qiming Wu, Zhenli Li, Yongyi Zeng, Hongbing Ji, Zhixiong Cai, Xiaolong Liu

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引用次数: 0

Abstract

Background: The abscopal effect, regression of unirradiated tumors after localized radiotherapy, is rare. Whether hypofractionated radiotherapy (HFRT) plus the innate immune agonist polyinosinic-polycytidylic acid [Poly(I:C)] amplifies systemic antitumor immunity in advanced hepatocellular carcinoma is unclear.

Methods: In this single-arm, phase 2 trial (ChiCTR2100053441), 37 patients received HFRT plus subcutaneous Poly(I:C); 33 were response evaluable. Outcomes were compared with 33 propensity score-matched patients treated with HFRT alone. The primary endpoint was the objective response rate per RECIST v.1.1; secondary endpoints included progression-free survival, overall survival, and safety; and abscopal response was prespecified. Mechanisms were explored by single-cell RNA sequencing and flow cytometry in patients and by CD8 depletion and CD28 blockade in mice.

Findings: HFRT plus Poly(I:C) was well tolerated; it was associated with a higher objective response rate (54.5% vs. 21.2%; p = 0.011) and abscopal response rate (45.0% vs. 10.5%; p = 0.042) as well as longer progression-free survival (8.4 vs. 4.6 months; adjusted hazard ratio = 0.542; p = 0.042) and overall survival (not reached vs. 13.6 months; adjusted hazard ratio = 0.386; p = 0.011) vs. HFRT alone. The progression-free survival benefit was also higher in patients concurrently receiving tyrosine kinase inhibitors (p for interaction = 0.013). Peripheral CD8⁺CD28⁺ T cell expansion correlated with abscopal tumor control; in mice, CD8⁺ T cells and CD28 co-stimulation were required for this effect.

Conclusions: HFRT plus Poly(I:C) showed promising systemic antitumor activity with manageable safety in advanced hepatocellular carcinoma, with CD8⁺CD28⁺ T cells as an immune correlate of response. These exploratory findings warrant confirmation in randomized trials.

Funding: The National Natural Science Foundation of China.

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低分割放疗加Poly（I:C）治疗晚期肝细胞癌的全身抗肿瘤反应：2期试验

背景：局部放射治疗后未照射肿瘤的退行是罕见的。低分割放疗（HFRT）加先天免疫激动剂聚肌苷-多胞酸（Poly(I:C)）是否能增强晚期肝癌患者的全身抗肿瘤免疫尚不清楚。方法：在这项单臂2期试验（ChiCTR2100053441）中，37例患者接受HFRT +皮下Poly(I:C)；33例反应可评价。将33名倾向评分匹配的患者单独接受HFRT治疗的结果进行比较。主要终点是RECIST v.1.1标准的客观缓解率；次要终点包括无进展生存期、总生存期和安全性；抽象响应是预先指定的。通过患者单细胞RNA测序和流式细胞术以及小鼠CD8缺失和CD28阻断来探索机制。结果：HFRT + Poly（I:C）耐受性良好；客观缓解率（54.5% vs. 21.2%, p = 0.011）和抽象缓解率（45.0% vs. 10.5%, p = 0.042）较高，无进展生存期（8.4 vs. 4.6个月，校正风险比= 0.542,p = 0.042）和总生存期（未达到vs. 13.6个月，校正风险比= 0.386,p = 0.011）均与单纯HFRT相关。同时接受酪氨酸激酶抑制剂治疗的患者的无进展生存获益也更高（相互作用p = 0.013）。外周CD8+CD28+ T细胞扩增与体外肿瘤控制相关在小鼠中，需要CD8+ T细胞和CD28共同刺激才能达到这种效果。结论：HFRT + Poly（I:C）在晚期肝细胞癌中显示出有希望的全身抗肿瘤活性和可控的安全性，CD8+CD28+ T细胞是免疫应答的相关因素。这些探索性发现值得在随机试验中得到证实。资助项目：国家自然科学基金。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.