INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, 56 Rue Leblanc, Paris 75015, France.
Equipe Labellisée Ligue Contre le Cancer, Paris 75015, France.
Nat Commun. 2017 May 24;8:15221. doi: 10.1038/ncomms15221.
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.
组织驻留记忆 T 细胞(Trm)代表了一种新的长寿记忆 T 细胞亚群,它们存在于组织中,不会再循环。尽管它们被认为是传染病中早期的免疫效应物,但它们在癌症免疫监视中的作用尚不清楚。在头颈部癌症的临床前模型中,我们表明,用黏膜载体 Shiga 毒素 B 亚单位进行鼻内疫苗接种可诱导局部 Trm 并抑制肿瘤生长。由于 Trm 不会再循环,我们通过并体实验证明了它们在癌症疫苗中的功效中的关键作用。TFGβ 的阻断减少了黏膜疫苗免疫后 Trm 的诱导,导致癌症疫苗的效果降低。为了将 Trm 在人类中的这种作用外推,我们表明在多变量分析中,Trm 的数量与肺癌的总生存率提高相关。Trm 的诱导可能代表癌症疫苗疗效的新替代生物标志物。这项研究还呼吁开发旨在诱导它们的疫苗策略。