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 (1). As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments (2). Blockade of TFGβ decreases the induction of Trm after mucosal vaccine immunization, resulting in the lower efficacy of cancer vaccine. In contrast, using fingolimod (FTY720) which blocked the recruitment of circulating effector cells, we demonstrate the major role of Trm over effector T cells to control tumor growth following cancer vaccine administration. 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 a therapeutic HPV cancer vaccine. This study also argues for the development of vaccine strategies designed to elicit them.
(1) Sandoval, F., Terme, M., Nizard, M., Badoual, C., Bureau, M.-F., Freyburger, L., Clement, O., Marcheteau, E., Gey, A., Fraisse, G., et al. (2013). Mucosal imprinting of vaccine-induced CD8+ T cells is crucial to inhibit the growth of mucosal tumors. Sci. Transl. Med. 5, 172ra20.
(2) Nizard, M., Roussel, H., Diniz, M.O., Karaki, S., Tran, T., Voron, T., Dransart, E., Sandoval, F., Riquet, M., Rance, B., et al. (2017). Induction of resident memory T cells enhances the efficacy of cancer vaccine. Nat. Commun. 8, 15221.