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大型T细胞克隆表达免疫检查点在多发性骨髓瘤进化过程中增加,并预测治疗耐药性

Cirino Botta^1,2, Cristina Perez³, Marta Larrayoz³

¹Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy. cirino.botta@unipa.it.

Nature communications

|September 20, 2023

概括

多发性骨髓瘤 (MM) 的T细胞功能障碍涉及免疫检查点. 针对这些检查点并使用CD27比率可以改善MM治疗结果.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
基因组学就是基因组学.

背景情况:

对抗瘤免疫力来说,T细胞的识别是至关重要的.
了解T细胞多样性是优化PD-1阻断等免疫疗法的关键,特别是在多发性髓瘤 (MM) 中.

研究的目的:

在健康成年人和患有前体和成熟MM的患者的骨髓中表征T细胞多样性.
确定与功能障碍相关的T细胞表型,并探索MM中潜在的治疗点和预后标志物.

主要方法:

用单细胞RNA和T细胞受体测序来分析健康人和MM患者的骨髓T细胞.
使用流细胞计量来评估CD27阴性和CD27阳性T细胞的比例.
在MM的小鼠模型中测试了PD-1+LAG3或PD-1+TIGIT的双重向.

主要成果:

在MM患者中,大型T细胞克隆表现出多个免疫检查点,表明潜在的功能障碍.
用LAG3或TIGIT对PD-1的双重阻断在小鼠模型中部分恢复了T细胞功能.
CD27阴性和CD27阳性T细胞的比率作为克隆T细胞扩张的替代品,是MM患者的独立预后因素.

结论:

鉴别T细胞表型和多样性对于理解MM免疫病原发生和治疗反应至关重要.
针对PD-1,LAG3和TIGIT等免疫检查点的联合向显示出恢复MM中T细胞功能的前景.
CD27 T细胞比率是MM患者的潜在预后生物标志物,特别是那些接受基于lenalidomide的疗法的人.

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