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

J. Grabowska, A. J. Affandi, D. van Dinther, M. K. Nijen Twilhaar, K. Olesek, L. Hoogterp, M. Ambrosini, D. A. M. Heijnen, L. Klaase, A. Hidalgo, K. Asano, P. R. Crocker, G. Storm, Y. van Kooyk, J. M. M. den Haan (Lead / Corresponding author)

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    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.

    Original languageEnglish
    Pages (from-to)309-320
    Number of pages12
    JournalJournal of Controlled Release: Official Journal of the Controlled Release Society, and of the Japan Society of Drug Delivery System
    Volume331
    Early online date22 Jan 2021
    DOIs
    Publication statusE-pub ahead of print - 22 Jan 2021

    Keywords

    • Liposomes
    • CD169
    • Siglec-1
    • Macrophage
    • Dendritic cell
    • T cell response

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