Sialic acid removal from dendritic cells improves antigen cross presentation and boosts anti-tumor immune responses

Mariana Silva, Zélia Silva, Graca Marques, Tiago Ferro, Marcia Goncalves, Mauro Monteiro, Sandra J van Vliet, Elodie Mohr, Andreia C Lino, Alexandra R Fernandes, Flavia A. Lima, Yvette van Kooyk, Teresa Matos, Carlos E Tadokoro, Paula A Videira

Research output: Contribution to journalArticle

Abstract

Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated antitumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation gP100(28-288) specific CD8(+) cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4(+) and CD8(+) T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs' ability to elicit T cell-mediated antitumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.

Original languageEnglish
Pages (from-to)41053-41066
Number of pages14
JournalOncotarget
Volume7
Issue number27
DOIs
Publication statusPublished - 5 Jul 2016

Keywords

  • dendritic cells
  • sialic acid
  • antigen cross-presentation
  • Th1-polarization
  • anti-tumor immunity
  • MHC CLASS-I
  • T-CELLS
  • INTERFERON-GAMMA
  • CLINICAL-USE
  • IMMUNOTHERAPY
  • MECHANISMS
  • MATURATION
  • IL-10
  • DIFFERENTIATION
  • RECOGNITION

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