Induction of resident memory T cells enhances the efficacy of cancer vaccine.
Induction of resident memory T cells enhances the efficacy of cancer vaccine.
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DOI：
10.1038/ncomms15221
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发表时间：
2017-05-24
影响因子：
16.6
通讯作者：
Tartour E
中科院分区：
文献类型：
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作者：
Nizard M;Roussel H;Diniz MO;Karaki S;Tran T;Voron T;Dransart E;Sandoval F;Riquet M;Rance B;Marcheteau E;Fabre E;Mandavit M;Terme M;Blanc C;Escudie JB;Gibault L;Barthes FLP;Granier C;Ferreira LCS;Badoual C;Johannes L;Tartour E
组织驻留记忆T细胞（Tissue-resident memory T cells，Trm）是一种新的长寿命记忆T细胞亚群，它们保留在组织中，不会再循环。虽然它们被认为是感染性疾病的早期免疫效应物，但它们在癌症免疫监视中的作用仍然未知。在头颈部癌的临床前模型中，我们发现鼻内接种粘膜载体（滋贺毒素的B亚基）诱导局部Trm并抑制肿瘤生长。由于Trm不能再循环，我们通过联体共生实验证明了它们在癌症疫苗效力中的关键作用。阻断TFGβ可降低粘膜疫苗免疫后Trm的诱导，从而降低肿瘤疫苗的免疫效果。为了推断Trm在人类中的这种作用，我们在多变量分析中表明Trm的数量与肺癌的更好的总生存率相关。Trm的诱导可能代表癌症疫苗功效的新的替代生物标志物。这项研究还主张开发旨在引发它们的疫苗策略。驻留记忆T细胞（Trm）是保留在组织中的记忆T细胞。在这里，作者表明，在携带头颈癌的小鼠中，在粘膜接种后，需要诱导Trm细胞来控制肿瘤生长，并且人肺癌中的Trm细胞与更好的存活率相关。
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. Resident memory T cells (Trm) are memory T cells that remain in tissue. Here, the authors show that induction of Trm cells is required for control of tumour growth following mucosal vaccination in mice bearing head and neck cancer and that Trm cells in human lung cancer correlates with a better survival.