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

诱导驻留记忆T细胞可增强癌症疫苗的疗效

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作者:Mevyn Nizard ,Hélène Roussel ,Mariana O Diniz ,Soumaya Karaki ,Thi Tran ,Thibault Voron ,Estelle Dransart ,Federico Sandoval ,Marc Riquet ,Bastien Rance ,Elie Marcheteau ,Elizabeth Fabre ,Marion Mandavit ,Magali Terme ,Charlotte Blanc ,Jean-Baptiste Escudie ,Laure Gibault ,Françoise Le Pimpec Barthes ,Clemence Granier ,Luis C S Ferreira ,Cecile Badoual ,Ludger Johannes ,Eric Tartour

Abstract

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.

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