Expression data from syngeneic Hepa1-6 model in C57Bl/6J mice. Expression data from syngeneic Hepa1-6 model in C57Bl/6J mice

Lenvatinib is an effective drug in advanced hepatocellular carcinoma (HCC). Its combination with the anti-PD1 immune checkpoint inhibitor pembrolizumab has achieved encouraging results in phase Ib and is currently being tested in phase III trials. Here, we aimed at exploring the molecular and immunomodulatory effects of lenvatinib alone or in combination with anti-PD1. We generated a syngeneic model of HCC in C57BL/6J mice and randomized the animals to receive placebo, lenvatinib, anti-PD1 or combination treatment. Transcriptomic analysis were performed to assess the expression profile of tumors from mice receiving each treatment strategy. Overall design: Tumors were collected 13 days post-randomization. Animals were euthanized 1 day after the last anti-PD1 dose and 2h after the last lenvatinib dose in accordance with pharmacodynamic studies (n=21). Gene expression analyses were conducted using the Clariom S Mouse Array (Affymetrix).

仑伐替尼（Lenvatinib）是治疗晚期肝细胞癌（hepatocellular carcinoma, HCC）的有效药物。其与抗PD-1免疫检查点抑制剂帕博利珠单抗（pembrolizumab）的联合疗法在Ib期临床试验中取得了令人鼓舞的成果，目前正处于III期临床试验阶段。本研究旨在探究仑伐替尼单药或联合抗PD-1疗法的分子与免疫调节作用。我们在C57BL/6J小鼠中构建了肝癌同源移植模型，并将实验动物随机分配至安慰剂组、仑伐替尼单药组、抗PD-1单药组及联合治疗组。通过转录组学分析，评估不同治疗策略下小鼠肿瘤的基因表达谱。实验设计概述：随机分组后第13天采集肿瘤样本。根据药效学研究要求，在末次抗PD-1给药后1天、末次仑伐替尼给药后2小时对动物实施安乐死（n=21）。基因表达分析采用Clariom S小鼠基因表达阵列（Affymetrix）完成。