Sialic acid removal from dendritic cells improves antigen cross-presentation and boosts anti-tumor immune responses
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Mariana Silva1,*, Zélia Silva1,6,*, Graça Marques1,*, Tiago Ferro1,6, Márcia Gonçalves1, Mauro Monteiro1, Sandra J. van Vliet2, Elodie Mohr4, Andreia C. Lino4, Alexandra R. Fernandes6,7, Flávia A. Lima1, Yvette van Kooyk2, Teresa Matos5, Carlos E. Tadokoro3,4,6,** and Paula A. Videira1,6,**
1 CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal
2 Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
3 Universidade Vila Velha, Espírito Santo, Brasil
4 IGC, Instituto Gulbenkian de Ciência, Oeiras, Portugal
5 StemLab, Cantanhede, Portugal
6 UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Portugal
7 CQE, Centro Química Estrutural, Instituto Superior Técnico, ULisboa, Lisboa, Portugal
* Co-first authorship
** Co-last authorship
Paula A. Videira, email:
Keywords: dendritic cells, sialic acid, antigen cross-presentation, Th1-polarization, anti-tumor immunity
Received: December 09, 2015 Accepted: April 16, 2016 Published: May 17, 2016
Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti-tumor 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 ofgp100280–288 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 anti-tumor 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.
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