Uptake routes of tumor-antigen MAGE-A3 by dendritic cells determine priming of naïve T-cell subtypes

Cancer Immunology, Immunotherapy : CII
Ines MoellerLeonora Houet

Abstract

Induction of tumor-antigen-specific T cells in active cancer immunotherapy is generally difficult due to the very low anti-tumoral precursor cytotoxic T cells. By improving tumor-antigen uptake and presentation by dendritic cells (DCs), this problem can be overcome. Focusing on MAGE-A3 protein, frequently expressed in many types of tumors, we analyzed different DC-uptake routes after additional coating the recombinant MAGE-A3 protein with either a specific monoclonal antibody or an immune complex formulation. Opsonization of the protein with antibody resulted in increased DC-uptake compared to the uncoated rhMAGE-A3 protein. This was partly due to Fcγ receptor-dependent internalization. However, unspecific antigen internalization via macropinocytosis also played a role. When analyzing DC-uptake of MAGE-A3 antigen expressed in multiple myeloma cell line U266, pretreatment with proteasome inhibitor bortezomib resulted in increased apoptosis compared to γ-irradiation. Bortezomib-mediated immunogenic apoptosis, characterized by elevated surface expression of hsp90, triggered higher phagocytosis of U266 cells by DCs involving specific DC-derived receptors. We further investigated the impact of antigen delivery on T-cell priming. Ind...Continue Reading

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Citations

Sep 5, 2013·Journal of Dermatological Science·Taisuke ItoYoshiki Tokura
Aug 1, 2014·Cancer Immunology, Immunotherapy : CII·Tim LuetkensDjordje Atanackovic
Aug 27, 2015·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Jean-Louis PujolFrédéric F Lehmann
Jun 20, 2015·Journal of Translational Medicine·Sara YousefDjordje Atanackovic
May 14, 2016·International Journal of Cancer. Journal International Du Cancer·Yusuke OjiHaruo Sugiyama
Apr 9, 2017·The Journal of Experimental Medicine·Christian H K LehmannDiana Dudziak
Sep 10, 2014·International Journal of Cancer. Journal International Du Cancer·Lei WangMichael Schmitt
Aug 31, 2019·Nature Reviews. Immunology·Stefanie K WculekDavid Sancho
Aug 17, 2019·Frontiers in Cell and Developmental Biology·Ken Maes, Karine Breckpot
Sep 7, 2018·Experimental and Therapeutic Medicine·Wen JianYing Xue
Aug 19, 2017·Cancer Research·Victor A GallElizabeth A Mittendorf
Jun 25, 2020·Seminars in Cancer Biology·Raghwendra Pratap SinghRashmi Kumar
Feb 21, 2018·Trends in Cancer·Mansi Saxena, Nina Bhardwaj

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