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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Inmunoterapia > DA - CIMA - Oncología - Inmunoterapia - Artículos de Revista >

Clinical implications of antigen transfer mechanisms from malignant to dendritic cells: Exploiting cross-priming
Authors: Arina, A. (Ainhoa)
Tirapu, I. (Íñigo)
Alfaro, C. (Carlos)
Rodriguez-Calvillo, M. (Mercedes)
Mazzolini, G. (Guillermo)
Inoges, S. (Susana)
Lopez, A. (Ascensión)
Feijoo, E. (Esperanza)
Bendandi, M. (Maurizio)
Melero, I. (Ignacio)
Keywords: Antigen Presentation/physiology
Dendritic Cells/immunology
Neoplastic Cells, Circulating/immunology
Issue Date: 2002
Publisher: Elsevier
Publisher version: http://www.sciencedirect.com/science/article/pii/S0301472X02009566
ISSN: 1873-2399
Citation: Arina A, Tirapu I, Alfaro C, Rodriguez-Calvillo M, Mazzolini G, Inoges S, et al. Clinical implications of antigen transfer mechanisms from malignant to dendritic cells. exploiting cross-priming. Exp Hematol 2002 Dec;30(12):1355-1364.
Abstract
Expansion and activation of cytolytic T lymphocytes bearing high-affinity T-cell receptors specific for tumor antigens is a major goal of active cancer immunotherapy. Physiologically, T cells receive promitotic and activating signals from endogenous professional antigen-presenting cells (APC) rather than directly from malignant cells. This phenomenon fits with the broader concept of cross-presentation that earlier was demonstrated for minor histocompatibility and viral antigens. Many mechanisms have been found to be capable of transferring antigenic material from malignant cells to APC so that it can be processed and subsequently presented by MHC class I molecules expressed on APC. Dendritic cells (DC) are believed to be the most relevant APC mediating cross-presentation because they can take up antigens from apoptotic, necrotic, and even intact tumor cells. There exist specific molecular mechanisms that ensure this transfer of antigenic material: 1) opsonization of apoptotic bodies; 2) receptors for released heat shock proteins carrying peptides processed intracellularly; 3) Fc receptors that uptake immunocomplexes and immunoglobulins; and 4) pinocytosis. DC have the peculiar capability of reentering the exogenously captured material into the MHC class I pathway. Exploitation of these pieces of knowledge is achieved by providing DC with complex mixtures of tumor antigens ex vivo and by agents and procedures that promote infiltration of malignant tissue by DC. The final outcome of DC cross-presentation could be T-cell activation (cross-priming) but also, and importantly, T-cell tolerance contingent upon the activation/maturation status of DC. Artificial enhancement of tumor antigen cross-presentation and control of the immune-promoting status of the antigen-presenting DC will have important therapeutic implications in the near future.
Permanent link: http://hdl.handle.net/10171/18753
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista
DA - CIMA - Oncología - Inmunoterapia - Artículos de Revista
DA - CUN - Hematología y Hemoterapia - Artículos de revista
DA - CUN - Área de Terapia Celular - Artículos de revista
DA - Medicina - Hematología - Artículos de revista

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