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PD-L1+巨细胞抑制T细胞介导的抗癌免疫力

Peng Liu^1,2, Liwei Zhao^1,2, Guido Kroemer^1,2,3

¹Centre de Recherche des Cordeliers, Equipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Institut Universitaire de France, Paris, France.

|April 9, 2024

概括

自体DC疫苗增加了免疫抑制性巨细胞,阻碍了疗效. 将DC疫苗与抗PD-L1疗法结合起来,通过阻断PD-L1来克服这一问题,从而实现CD8+细胞毒性T淋巴细胞介导的瘤抑制.

科学领域:

免疫学免疫学免疫学
癌症治疗癌症治疗
疫苗学疫苗学疫苗学

背景情况:

基于自身树突细胞 (DC) 的疫苗可以增强抗瘤免疫力.
然而,DC疫苗可能无意中促进免疫抑制瘤微环境.
已知PD-L1+瘤相关巨细胞 (TAM) 抑制T细胞反应.

研究的目的:

调查基于DC的疫苗对TAM群体的影响.
评估克服疫苗诱导免疫抑制的策略.
为了确定将DC疫苗与免疫检查点抑制剂结合的疗效.

主要方法:

小鼠接受了基于直流的自主疫苗.
瘤和淋巴结组织被分析为PD-L1+TAM.
治疗疗效评估与抗PD-1或抗PD-L1抗体结合使用.
测量了CD8+细胞毒性T淋巴细胞 (CTL) 活性.

主要成果:

DC疫苗接种导致瘤中的PD-L1+TAM增加和淋巴结排水.
这种PD-L1+TAM的增加削弱了疫苗的疗效.
与抗PD-L1的联合治疗,但不是单独抗PD-1,恢复了CTL介导的瘤抑制.
确定了一个PD-L1检查点封锁战略.

结论:

DC疫苗可以在TAM中诱导一种免疫抑制的表型.
PD-L1+ TAM有助于T细胞耗尽并限制疫苗的有效性.
将DC疫苗与抗PD-L1疗法结合起来是一个有希望的策略,以克服TAM介导的免疫抑制并增强抗瘤免疫力.

关键词:

癌症癌症癌症癌症疫苗 DC DC 的疫苗.免疫治疗是一种免疫疗法.

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