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在腺囊性癌症中,HLA类I的可逆下调可逆

Annie Li¹, Bianca L Gonda¹, Elizabeth M Codd¹

¹Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Journal for immunotherapy of cancer

|April 20, 2025

概括

腺素性囊性癌 (ACC) 是免疫学上冷的,由于β-2-微型血球蛋白 (B2M) /人类白细胞抗原 (HLA) 的低I类表达. 刺痛激动剂可以恢复B2M/HLA表达,为ACC提供潜在的新免疫疗法.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
癌症基因组学癌症基因组学

背景情况:

腺状囊性癌 (ACC) 对当前的全身疗法反应不佳.
复发或转移的ACC具有有限的有效治疗选择,导致高死亡率.

研究的目的:

为了研究ACC瘤和转移的免疫场景.
确定导致ACC对免疫疗法的耐药性的机制.
探索针对ACC的新型治疗策略.

主要方法:

多重免疫光学 (mIF) 和单细胞RNA测序 (scRNA-seq) 用于分析瘤免疫微环境.
空间转录组学用于映射转移性病变中的基因表达.
用干扰素-γ和STING激动剂进行ACC组织的体外治疗.
在ACC患者中,STING激动剂 (dazostinag) 加上 pembrolizumab 的第一阶段临床研究.

主要成果:

ACC瘤在免疫学上是"冷"的,T淋巴细胞透率低,PD-L1表达率低.
一个引人注目的发现是,在ACC中,β-2-微型球蛋白 (B2M) 和人类白细胞抗原 (HLA) 的I类表达非常低.
在体外和体内研究表明,STING激动剂可以调节B2M/HLA I类表达.
一位患有转移性ACC的患者对dazostinag加上pembrolizumab的治疗显示出部分反应 (70%的瘤减少).

结论:

低B2M/HLA I类表达可能导致ACC的免疫逃避和对免疫检查点抑制剂 (ICI) 的反应不佳.
药理上激活STING通路可以恢复B2M/HLA在ACC中的表达.
刺痛激动剂代表了ACC免疫治疗的有希望的治疗途径.

关键词:

头部和部癌症头部和部癌症人类白细胞抗原 - - HLA 免疫调节器免疫调节器主要组织相容性复杂 - - MHC.

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