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deltaHED预测PD-1阻断疗法中的生存和免疫逃避:跨三种癌症类型的多队列研究

Jianying Xu^1,2, Xiaoli Wei¹, Jicheng Yao³

¹Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Clinical and translational medicine

|January 28, 2026

概括

一个新的度量,deltaHED,通过分析HLA类I (HLA-I) 的等位基因来测量免疫分歧. 高德尔塔HED预测,在接受PD-1阻断免疫疗法治疗各种癌症的患者中,结果较差.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
遗传学是一个遗传学.

背景情况:

在癌症免疫治疗中,HLA类I (HLA-I) 介导免疫的作用尚未完全理解.
有效的癌症免疫疗法依赖于瘤和宿主免疫系统之间的复杂相互作用.

研究的目的:

引入和验证deltaHED,一种新的度量衡量生殖线和瘤获得的HLA-I等位基因之间的进化分歧.
评估deltaHED在接受癌症免疫治疗的患者的预后相关性.

主要方法:

整体外组测序用于分析三组独立患者的deltaHED:复发性/转移性鼻癌 (RM/NPC),黑色素瘤和食道状细胞癌 (ESCC).
患者接受PD-1单疗或PD-1加化疗.
研究了deltaHED,瘤突变负担,新抗原负载和生存结果 (无进展生存和整体生存) 之间的相关性.

主要成果:

高德尔塔HED与瘤突变负荷和新抗原负载 (p < .001) 的增加显著相关.
在接受PD-1阻塞治疗的患者中,高的deltaHED预测了更差的无进展生存率和整体生存率在所有三种癌症类型中.
在ESCC中,高deltaHED的负预后关联是针对免疫治疗组的特异性.

结论:

deltaHED是一个临床相关的生物标志物,反映了免疫分歧.
这一指标整合了遗传和体质免疫遗传变异.
deltaHED有可能增强患者分层和个性化癌症免疫治疗策略.

关键词:

抗原呈现的呈现方式.反编程死亡-1免疫疗法食管状细胞癌的癌症人类白细胞抗原I类鼻癌鼻癌鼻癌

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