瘤载体宿主中鼻巨细胞的功能障碍诱导了对免疫治疗的抵抗力
Toshiki Anami1,2, Cheng Pan1, Yukio Fujiwara1
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Cancer science
|November 3, 2023
概括
表达CD169的鼻腔巨对于抗瘤免疫力和免疫疗法的有效性至关重要. 纳林激活这些巨细胞,增强T细胞反应并抑制瘤生长,特别是与PD-L1阻断相结合时.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
- 巨细胞生物学 巨细胞生物学
背景情况:
- 在排水淋巴结 (DLNs) 中的鼻腔巨细胞在抗瘤免疫力中发挥作用.
- CD169 (Sialoadhesin) 标志着免疫刺激性巨细胞,是它们功能的关键.
- 了解巨细胞的作用对于改善癌症免疫疗法至关重要.
研究的目的:
- 为了研究鼻巨细胞在抗PD-L1抗体治疗中的作用.
- 为了评估纳林对鼻巨细胞和抗瘤免疫力的影响.
- 探索用纳林丁和抗PD-L1进行结合疗法,以增强瘤抑制.
主要方法:
- 利用小鼠模型 (MC38,E0771,MB49,LLC) 来评估瘤生长和免疫反应.
- 单独或组合使用抗编程死亡配体1 (PD-L1) 抗体和naringin.
- 枯竭的鼻巨细胞,以确定它们对治疗效果的必要性.
- 测量了细胞毒性T淋巴细胞 (CTL) 透和激活,以及巨细胞上的CD169表达.
主要成果:
- 在不同瘤模型中,抗PD-L1疗效不同,与CTL透和CD169+鼻腔巨水平相关.
- 鼻巨细胞的消耗取消了抗PD-L1的抗瘤作用.
- 纳林激活了鼻巨细胞,在特定模型中抑制了瘤生长,并增强了CTL反应.
- 与纳林金和抗PD-L1联合治疗在MB49模型中协同抑制了瘤生长.
结论:
- 在DLN中的CD169阳性鼻巨细胞对于抗瘤免疫反应和抗PD-L1治疗成功至关重要.
- 纳林因通过激活鼻巨细胞和促进CTL反应,促进抗瘤免疫力.
- 向鼻巨细胞激活是增强癌症免疫疗法的有希望的策略.
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