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

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

Research output: Contribution to journalArticlepeer-review


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
Issue number27
Publication statusPublished - 5 Jul 2016


  • dendritic cells
  • sialic acid
  • antigen cross-presentation
  • Th1-polarization
  • anti-tumor immunity
  • IL-10


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