Liposome induction of CD8+ T cell responses depends on CD169+ macrophages and Batf3-dependent dendritic cells and is enhanced by GM3 inclusion

J Control Release. 2021 Mar 10;331:309-320. doi: 10.1016/j.jconrel.2021.01.029. Epub 2021 Jan 22.

Abstract

Cancer vaccines aim to efficiently prime cytotoxic CD8+ T cell responses which can be achieved by vaccine targeting to dendritic cells. CD169+ macrophages have been shown to transfer antigen to dendritic cells and could act as an alternative target for cancer vaccines. Here, we evaluated liposomes containing the CD169/Siglec-1 binding ligand, ganglioside GM3, and the non-binding ligand, ganglioside GM1, for their capacity to target antigens to CD169+ macrophages and to induce immune responses. CD169+ macrophages demonstrated specific uptake of GM3 liposomes in vitro and in vivo that was dependent on a functional CD169 receptor. Robust antigen-specific CD8+ and CD4+ T and B cell responses were observed upon intravenous administration of GM3 liposomes containing the model antigen ovalbumin in the presence of adjuvant. Immunization of B16-OVA tumor bearing mice with all liposomes resulted in delayed tumor growth and improved survival. The absence of CD169+ macrophages, functional CD169 molecules, and cross-presenting Batf3-dependent dendritic cells (cDC1s) significantly impaired CD8+ T cell responses, while B cell responses were less affected. In conclusion, we demonstrate that inclusion of GM3 in liposomes enhance immune responses and that splenic CD169+ macrophages and cDC1s are required for induction of CD8+ T cell immunity after liposomal vaccination.

Keywords: CD169; Dendritic cell; Liposomes; Macrophage; Siglec-1; T cell response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Dendritic Cells
  • Liposomes*
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin
  • T-Lymphocytes*

Substances

  • Liposomes
  • Ovalbumin