CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD74 与炎症性肿瘤免疫微环境相关，并可预测实体瘤患者对 PD-1/CTLA-4 双特异性抗体的应答
英文原题：CD74 is associated with inflamed tumor immune microenvironment and predicts responsiveness to PD-1/CTLA-4 bispecific antibody in patients with solid tumors.
查看英文原题
CD74 is associated with inflamed tumor immune microenvironment and predicts responsiveness to PD-1/CTLA-4 bispecific antibody in patients with solid tumors.
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研究概要
我们的研究结果表明，CD74 是晚期实体瘤中 AK104 治疗反应的一个有前景的预测生物标志物。试验注册号 NCT03261011。
研究思路结论见上方概要
Cadonilimab (AK104) 是一种首创的四价双特异性抗体，靶向 PD-1 和 CTLA-4，显示出可控的安全性特征和良好的临床获益。本研究旨在识别临床应答的生物标志物，并探索 AK104 治疗晚期实体瘤时肿瘤微环境中的免疫反应。
对21例患者配对治疗前后肿瘤组织的基因表达谱进行了分析。评估了基因表达水平与临床疗效或预后的关联，随后利用已发表数据集通过Kaplan-Meier估计的log-rank检验进行了验证。对AK104治疗前后肿瘤微环境的免疫谱进行了比较分析。使用多重免疫组化对TIL（肿瘤浸润淋巴细胞）进行了可视化。通过免疫组化检测蛋白表达进一步验证了CD74的预测价值。
基线CD74基因表达与患者良好结局相关（总生存期[OS]，HR = 0.33，95% CI 0.11-1.03，p = 0.0463），这一结果在已发表的数据集中得到进一步证实。基线CD74基因高表达的肿瘤更可能呈现免疫炎症型微环境。AK104有效增强了肿瘤微环境中免疫细胞的浸润。此外，基线CD74蛋白高表达（CD74染色免疫细胞占肿瘤面积≥ 10%）与更好的无进展生存期（HR = 0.21，95% CI 0.06-0.68，p = 0.0065）和OS（HR = 0.35，95% CI 0.12-1.08，p = 0.0615）相关。
展开英文摘要原文
Baseline CD74 gene expression was associated with favorable patient outcomes (overall survival [OS], HR = 0.33, 95% CI 0.11-1.03, p = 0.0463), which was further confirmed with the published datasets. Tumors with high CD74 gene expression at baseline were more likely to exhibit an immune-inflamed microenvironment. AK104 efficiently enhanced the infiltration of immune cells in the tumor microenvironment. Additionally, high CD74 protein expression (≥ 10% of the tumor area occupied by CD74 stained immune cells) at baseline was associated with better progressive-free survival (HR = 0.21, 95% CI 0.06-0.68, p = 0.0065) and OS (HR = 0.35, 95% CI 0.12-1.08, p = 0.0615).
Our findings demonstrate that CD74 is a promising predictive biomarker for AK104 therapeutic response in advanced solid tumors. Trial registration number NCT03261011.
论文信息
- 作者
- Wang J、Li X、Xiao G、Desai J、Frentzas S、Wang ZM、Xia Y、Li B
- 第一作者单位
- Research and Development Department, Akeso Biopharma Inc, Zhongshan, Guangdong, China.China
- 通讯作者单位
- Research and Development Department, Akeso Biopharma Inc, Zhongshan, Guangdong, China. baiyong.li@akesobio.com.China
- 期刊
- Cancer immunology, immunotherapy : CII2024 Jan 27
- 原文标识
- PubMed 38280003 · DOI 10.1007/s00262-023-03604-2
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