Oncotarget

Research Papers:

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 _

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Oncotarget. 2016; 7:41053-41066. doi: 10.18632/oncotarget.9419

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Abstract

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

Correspondence to:

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

Abstract

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.

Author Information

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
Primary Contact  _


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