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

增强抗肿瘤免疫需要驻留 CD8+ T 细胞和循环记忆 CD8+ T 细胞之间的相互作用

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作者:Michel Enamorado, Salvador Iborra, Elena Priego, Francisco J Cueto, Juan A Quintana, Sarai Martínez-Cano, Ernesto Mejías-Pérez, Mariano Esteban, Ignacio Melero, Andrés Hidalgo, David Sancho

Abstract

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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