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.
Highlights
The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse
We demonstrate that circulating CD8 þ T cells and T cells with a resident memory (Trm) cells cooperate in anti-tumour immunity
Whereas intraperitoneal (i.p.) infection with recombinant vaccinia virus (rVACV)-OVA was inefficient for the generation of Trm cells in the skin or the lung, skin scarification (s.s.) in the tail promoted Trm cells in the infection site and in a distant cutaneous site, and intranasal (i.n.) infection induced Trm cells in the lung (Fig. 1b–d and Supplementary Fig. 1b–d)
Summary
The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Anti-PD-1 treatment promotes infiltration of transferred Tcm cells within tumours, improving anti-tumour immunity. Batf3-dependent dendritic cells are essential for reactivation of circulating memory anti-tumour response. Optimal generation of Trm cells requires Batf3-dependent dendritic cells (DCs) during priming following VACV infection[13]. Recent results suggest that vaccination routes that promote generation of Trm cells could be more effective for anti-tumour response[22,23]. These findings prompted us to analyse the relative contribution and plasticity of circulating memory CD8 þ T cells and Trm cells in a model of anti-tumour vaccination. Knowledge on the generation of optimal memory against tumour antigens is essential for improved cancer immunotherapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
