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Nat Commun. 2017 Jul 17;8:16073. doi: 10.1038/ncomms16073.

Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells.

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Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernández Almagro, 3, Madrid 28029, Spain.
Universidad Autónoma de Madrid, Arzobispo Morcillo 4, Madrid 28029, Spain.
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Darwin 3, Madrid 28049, Spain.
Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 31008 Pamplona, Spain.
University Clinic, University of Navarra and Instituto de Investigación Sanitaria de Navarra (IdISNA), Pío XII, 55, 31008 Pamplona, Spain.
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität, Pettenkoferstrasse 9, 80336 Munich, Germany.


The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8+ T cells with a resident memory (Trm) phenotype correlates with improved survival. However, the interplay of circulating CD8+ T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy. Transferred central memory T cells (Tcm) generate Trm cells following viral infection or tumour challenge. Anti-PD-1 treatment promotes infiltration of transferred Tcm cells within tumours, improving anti-tumour immunity. Moreover, Batf3-dependent dendritic cells are essential for reactivation of circulating memory anti-tumour response. Our findings show the plasticity, collaboration and requirements for reactivation of memory CD8+ T cells subsets needed for optimal tumour vaccination and immunotherapy.

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