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Tumor associated MUC1 carried by microvesicles is cross-processed by dendritic cells generating CD8+ T cell response

Tumor associated MUC1 carried by microvesicles is cross-processed by dendritic cells generating... Zizzari et al. Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P140 http://www.immunotherapyofcancer.org/content/1/S1/P140 POSTER PRESENTATION Open Access Tumor associated MUC1 carried by microvesicles is cross-processed by dendritic cells generating CD8+ T cell response 1* 1 1 1 1 1 Ilaria G Zizzari , Federico Battisti , Chiara Napoletano , Hassan Rahimi , Salvatore Caponnetto , Paola Martufi , 1 2 3 1 1 Stefania Salvati , Morena Antonilli , Francesca Belleudi , Marianna Nuti , Aurelia Rughetti From Society for Immunotherapy of Cancer 28th Annual Meeting National Harbor, MD, USA. 8-10 November 2013 Authors’ details The induction of an efficacious anti-tumor immune Department of Experimental Medicine, Sapienza University, Rome, Italy. response (IR) requires the cross-processing and presen- Department of Gynaecology and Obstetrics, Sapienza University, Rome, Italy. tation of tumor antigen by Dendritic Cells (DCs). Block Department of Molecular Medicine, Sapienza University, Rome, Italy. of endocytated tumor associated antigen (TAA) in the Published: 7 November 2013 early compartments of the intracellular processing machinery shifts the IR towards a Th2 balance. MUC1 is one of the most relevant tumor associated glycopro- doi:10.1186/2051-1426-1-S1-P140 tein expressed by epithelial cells and its immunogenicity Cite this article as: Zizzari et al.: Tumor associated MUC1 carried by is altered by the glycosylation profile. Moreover soluble microvesicles is cross-processed by dendritic cells generating CD8+ T cell response. Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P140. MUC1 antigen has shown to be stucked in endolysoso- mal compartment of DCs thus inducing mostly a Th2 response. Objective of this study was to investigate whether glycosylation pattern and MUC1 bound to microvesicles could influence the antigen processing by DCs. MUC1 as soluble molecule, independently by the glycosylation profile, appears to be blocked in the pre- endosomal compartment. Receptor-mediated endocyto- sis pushes further the processing in the HLAII compart- ment. Cross-processing of MUC1 in HLAI compartment is observed only when MUC1 is carried by microvesicles (MUC1-MVs). Moreover only DCs stimulated with MUC1-MVs areable toinduceIFN-g production by MUC1 specific CD8+T cells. The distinct processing of Submit your next manuscript to BioMed Central the MUC1 membrane bound is accompanied by degly- and take full advantage of: cosylation processes thus generating Tn-MUC1 immu- nogenic glycoforms. These results show that MUC1 • Convenient online submission undergoes to alternative processing pathways depending • Thorough peer review by its form of release (MVs vs soluble) thus modifying • No space constraints or color figure charges MUC1 immunogenicity. Moreover these experimental • Immediate publication on acceptance evidence can be important to design efficacious glycoan- • Inclusion in PubMed, CAS, Scopus and Google Scholar tigen formulations for DC-based cancer vaccines. • Research which is freely available for redistribution Submit your manuscript at Department of Experimental Medicine, Sapienza University, Rome, Italy www.biomedcentral.com/submit Full list of author information is available at the end of the article © 2013 Zizzari et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal for ImmunoTherapy of Cancer Springer Journals

Tumor associated MUC1 carried by microvesicles is cross-processed by dendritic cells generating CD8+ T cell response

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Publisher
Springer Journals
Copyright
Copyright © 2013 by Zizzari et al; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Oncology
eISSN
2051-1426
DOI
10.1186/2051-1426-1-S1-P140
Publisher site
See Article on Publisher Site

Abstract

Zizzari et al. Journal for ImmunoTherapy of Cancer 2013, 1(Suppl 1):P140 http://www.immunotherapyofcancer.org/content/1/S1/P140 POSTER PRESENTATION Open Access Tumor associated MUC1 carried by microvesicles is cross-processed by dendritic cells generating CD8+ T cell response 1* 1 1 1 1 1 Ilaria G Zizzari , Federico Battisti , Chiara Napoletano , Hassan Rahimi , Salvatore Caponnetto , Paola Martufi , 1 2 3 1 1 Stefania Salvati , Morena Antonilli , Francesca Belleudi , Marianna Nuti , Aurelia Rughetti From Society for Immunotherapy of Cancer 28th Annual Meeting National Harbor, MD, USA. 8-10 November 2013 Authors’ details The induction of an efficacious anti-tumor immune Department of Experimental Medicine, Sapienza University, Rome, Italy. response (IR) requires the cross-processing and presen- Department of Gynaecology and Obstetrics, Sapienza University, Rome, Italy. tation of tumor antigen by Dendritic Cells (DCs). Block Department of Molecular Medicine, Sapienza University, Rome, Italy. of endocytated tumor associated antigen (TAA) in the Published: 7 November 2013 early compartments of the intracellular processing machinery shifts the IR towards a Th2 balance. MUC1 is one of the most relevant tumor associated glycopro- doi:10.1186/2051-1426-1-S1-P140 tein expressed by epithelial cells and its immunogenicity Cite this article as: Zizzari et al.: Tumor associated MUC1 carried by is altered by the glycosylation profile. Moreover soluble microvesicles is cross-processed by dendritic cells generating CD8+ T cell response. Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P140. MUC1 antigen has shown to be stucked in endolysoso- mal compartment of DCs thus inducing mostly a Th2 response. Objective of this study was to investigate whether glycosylation pattern and MUC1 bound to microvesicles could influence the antigen processing by DCs. MUC1 as soluble molecule, independently by the glycosylation profile, appears to be blocked in the pre- endosomal compartment. Receptor-mediated endocyto- sis pushes further the processing in the HLAII compart- ment. Cross-processing of MUC1 in HLAI compartment is observed only when MUC1 is carried by microvesicles (MUC1-MVs). Moreover only DCs stimulated with MUC1-MVs areable toinduceIFN-g production by MUC1 specific CD8+T cells. The distinct processing of Submit your next manuscript to BioMed Central the MUC1 membrane bound is accompanied by degly- and take full advantage of: cosylation processes thus generating Tn-MUC1 immu- nogenic glycoforms. These results show that MUC1 • Convenient online submission undergoes to alternative processing pathways depending • Thorough peer review by its form of release (MVs vs soluble) thus modifying • No space constraints or color figure charges MUC1 immunogenicity. Moreover these experimental • Immediate publication on acceptance evidence can be important to design efficacious glycoan- • Inclusion in PubMed, CAS, Scopus and Google Scholar tigen formulations for DC-based cancer vaccines. • Research which is freely available for redistribution Submit your manuscript at Department of Experimental Medicine, Sapienza University, Rome, Italy www.biomedcentral.com/submit Full list of author information is available at the end of the article © 2013 Zizzari et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal

Journal for ImmunoTherapy of CancerSpringer Journals

Published: Nov 7, 2013

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