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

• Published in: Nature communications Vol. 8; no. 1; p. 16073
• Main Authors: Enamorado, Michel, Iborra, Salvador, Priego, Elena, Cueto, Francisco J, Quintana, Juan A, Martínez-Cano, Sarai, Mejías-Pérez, Ernesto, Esteban, Mariano, Melero, Ignacio, Hidalgo, Andrés, Sancho, David
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 17.07.2017; Nature Portfolio
• Subjects: Activation; Adaptation, Physiological - immunology; Animals; Antineoplastic Agents, Immunological - immunology; Antineoplastic Agents, Immunological - pharmacology; Basic-Leucine Zipper Transcription Factors - genetics; Cancer Vaccines - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Immunity; Immunologic Memory - immunology; Immunological memory; Immunotherapy; Infections; Infiltration; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Melanoma, Experimental - immunology; Memory cells; Metastases; Mice; Mice, Knockout; PD-1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Repressor Proteins - genetics; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; Tumors; Vaccination; Vaccinia - immunology; Vaccinia virus
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms16073

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.