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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / immunology
  • Animals
  • Antineoplastic Agents, Immunological / immunology
  • Antineoplastic Agents, Immunological / pharmacology
  • Basic-Leucine Zipper Transcription Factors / genetics
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Immunologic Memory / immunology*
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Melanoma, Experimental / immunology*
  • Mice
  • Mice, Knockout
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Repressor Proteins / genetics
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Vaccinia / immunology*
  • Vaccinia virus

Substances

  • Antineoplastic Agents, Immunological
  • Basic-Leucine Zipper Transcription Factors
  • Cancer Vaccines
  • Programmed Cell Death 1 Receptor
  • Repressor Proteins
  • SNFT protein, mouse