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结质瘤相关的基甘驱动免疫抑制表型和髓状细胞的功能

Lenneke A M Cornelissen¹, Kim C M Santegoets¹, Esther D Kers-Rebel¹

¹Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

|July 27, 2024

概括

质母细胞细胞通过髓质衍生抑制细胞 (MDSC) 促进免疫抑制. 通过降低瘤细胞上的酸水平来准Siglec-酸轴,可以恢复抗瘤免疫力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
葡萄糖生物学葡萄糖生物学

背景情况:

质母细胞瘤 (GBM) 具有免疫抑制的瘤微环境.
骨髓衍生抑制细胞 (MDSCs) 是GBM免疫抑制中的关键参与者.
酸结合性免疫球蛋白类讲蛋白 (Siglecs) 作为糖免疫检查点,类似于PD-1.

研究的目的:

调查Siglec-酸相互作用在GBM微环境中的骨髓性免疫抑制中的作用.
探索针对这些相互作用的潜在治疗策略,以增强抗瘤免疫力.

主要方法:

共同培养人类单细胞与质母细胞瘤细胞.
评估单细胞上的CD163表达.
在质母细胞细胞脱离或Siglec受体触发后测量细胞因子分泌 (IL-6,TNFα).
使用抗Siglec-7和抗Siglec-9抗体.

主要成果:

质母细胞细胞在单细胞上诱导CD163的表达,从而导致免疫抑制.
质母细胞瘤细胞的消毒减少了CD163诱导,并增加了单细胞的促炎性细胞因子分泌 (IL-6,TNFα).
西格莱克特异性抗体触发了TNFα分泌量的减少,证实了西格莱克-酸轴的作用.

结论:

质母细胞诱导一个髓状免疫抑制表型,部分由Siglec-酸轴介导.
降低质母细胞瘤相关的酸水平可以部分逆转这种免疫抑制.
针对Siglec-酸轴是一个潜在的治疗策略,可以改善质母细胞瘤治疗结果.

关键词:

希格莱克斯 (Siglecs) 是一个符号.质瘤质瘤是一种骨髓状细胞是骨髓状细胞.类甘油是一种

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