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

TY - JOUR

T1 - Liposome induction of CD8+ T cell responses depends on CD169+ macrophages and Batf3-dependent dendritic cells and is enhanced by GM3 inclusion

AU - Grabowska, J.

AU - Affandi, A. J.

AU - van Dinther, D.

AU - Nijen Twilhaar, M. K.

AU - Olesek, K.

AU - Hoogterp, L.

AU - Ambrosini, M.

AU - Heijnen, D. A. M.

AU - Klaase, L.

AU - Hidalgo, A.

AU - Asano, K.

AU - Crocker, P. R.

AU - Storm, G.

AU - van Kooyk, Y.

AU - den Haan, J. M. M.

N1 - This work was supported by grants from the Dutch Cancer Society (VU2016-10449) to JMMdH, by NWO ZonMW TOP 91218024 to JMMdH and GS, and from the Phospholipid Research Center (JDH-2020-082/1-1) to JMMdH and YvK. We thank the staff of Amsterdam UMC Animal Facility (location VUmc) for animal care, especially R. van der Laan.

PY - 2021/3/10

Y1 - 2021/3/10

N2 - 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.

AB - 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.

KW - Liposomes

KW - CD169

KW - Siglec-1

KW - Macrophage

KW - Dendritic cell

KW - T cell response

U2 - 10.1016/j.jconrel.2021.01.029

DO - 10.1016/j.jconrel.2021.01.029

M3 - Article

C2 - 33493613

SN - 0168-3659

VL - 331

SP - 309

EP - 320

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -