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Induction of resident memory T cells enhances the efficacy of cancer vaccine

机译:驻留记忆T细胞的诱导增强癌症疫苗的功效

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Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments. Blockade of TFGβ decreases the induction of Trm after mucosal vaccine immunization, resulting in the lower efficacy of cancer vaccine. In order to extrapolate this role of Trm in humans, we show that the number of Trm correlates with a better overall survival in lung cancer in multivariate analysis. The induction of Trm may represent a new surrogate biomarker for the efficacy of cancer vaccine. This study also argues for the development of vaccine strategies designed to elicit them.
机译:组织驻留记忆T细胞(Trm)代表保留在组织中且不会循环的长寿命记忆T细胞的新子集。尽管它们被认为是传染病的早期免疫效应物,但它们在癌症免疫监测中的作用仍然未知。在头颈癌的临床前模型中,我们显示了鼻腔接种粘膜载体(志贺毒素的B亚基)可诱导局部Trm并抑制肿瘤生长。由于Trm不再循环,我们通过共生实验证明了它们在癌症疫苗效力中的关键作用。 TFGβ的阻滞减少了粘膜疫苗免疫后Trm的诱导,导致癌症疫苗的功效降低。为了推断Trm在人类中的这种作用,我们在多变量分析中显示Trm的数量与肺癌的较好总体生存率相关。 Trm的诱导可能代表了癌症疫苗功效的新替代生物标记。这项研究还主张开发旨在引诱它们的疫苗策略。

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