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Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy
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Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy
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Journal Article
Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy
2016
Overview
Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies.
We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation.
Results showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a TH1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of TH1 cytokines.
Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Antigen Presentation - genetics
/ Antigen Presentation - immunology
/ Antigens
/ Antigens, Neoplasm - immunology
/ Cancer
/ Cancer Vaccines - immunology
/ Cancer Vaccines - pharmacology
/ Cell Proliferation - physiology
/ Dendritic Cells - immunology
/ Female
/ Histocompatibility Antigens Class I - biosynthesis
/ Histocompatibility Antigens Class II - biosynthesis
/ Interferon-gamma - biosynthesis
/ Interleukin-10 - biosynthesis
/ Interleukin-12 - biosynthesis
/ Lymphocyte Activation - immunology
/ Major histocompatibility complex
/ Male
/ Medicine and Health Sciences
/ Mice
/ Mutation
/ Priming
/ Research and Analysis Methods
/ T cells
/ T-Lymphocytes, Cytotoxic - immunology
/ Tissue Extracts - pharmacology
/ Tumors
/ Vaccines
