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卵膜黑色素瘤免疫基因组学预测免疫疗法耐药性和易感性

Shravan Leonard-Murali^1,2,3,4, Chetana Bhaskarla^1,2,3, Ghanshyam S Yadav^1,2,3

¹UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.

Nature communications

|April 16, 2024

概括

转移性阴膜黑色素瘤抵抗免疫疗法. 研究人员确定了强效但被抑制的瘤透淋巴细胞,并开发了一个生物标志物来激活它们用于采用细胞疗法,为患者提供了新的希望.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
基因组学就是基因组学.

背景情况:

转移性皮肤黑色素瘤对免疫检查点抑制有反应.
发生在免疫特权眼睛的转移性皮膜黑色素瘤,在当前的免疫疗法中显示出有限的疗效.
了解皮膜黑色素瘤的耐药性机制对于开发有效的治疗方法至关重要.

研究的目的:

调查转移性阴膜黑色素瘤免疫检查点抑制剂耐药性背后的原因.
为了识别和表征瘤透淋巴细胞 (TILs) 在毛膜黑色素瘤转移.
开发策略,利用TILs在皮膜黑色素瘤中的抗瘤潜力.

主要方法:

使用临床基因组学和转录基因组学对100例人类毛膜色素瘤转移的综合分析.
评估瘤透性淋巴细胞 (TIL) 的功效和自身瘤特异性的评估.
开发用于TIL识别和ex vivo操纵的转录生物标志物.
在临床前模型中采用选择的TILs的采用转移.

主要成果:

超过50%的转移中含有具有强烈自身瘤特异性的TILs,尽管突变负担较低.
在瘤微环境中观察到较低的内T细胞受体 (TCR) 克隆性,即使在免疫治疗后.
开发了一种转录基因生物标志物来识别和分离静止的TILs.
通过转录组选择的TILs的采用转移证明了增强瘤免疫力的能力.

结论:

卵膜黑色素瘤转移带有瘤特异性TILs,这些TILs在功能上被抑制.
一个新的转录基因生物标志物使得治疗干预的强效TILs的选择成为可能.
经转录组选择的TIL收养转移显示出对治疗免疫疗法耐药的转移性乳膜黑色素瘤的希望.

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