Introduction 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. Matherials & Methods 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 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-gamma but only low levels of IL-10, indicating their ability to elicit a T(H)1-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 T(H)1 cytokines. Conclusion Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer.

Immunological characterization of whole tumour lysate-loaded dendritic cells for cancer immunotherapy / V. Rainone, C. Martelli, L. Ottobrini, M. Biasin, M. Borelli, G. Lucignani, D. Trabattoni, M. Clerici. - In: PLOS ONE. - ISSN 1932-6203. - 11:1(2016 Jan 21). [10.1371/journal.pone.0146622]

Immunological characterization of whole tumour lysate-loaded dendritic cells for cancer immunotherapy

V. Rainone
Primo
;
C. Martelli
Secondo
;
L. Ottobrini;M. Biasin;M. Borelli;G. Lucignani;D. Trabattoni
Penultimo
;
M. Clerici
Ultimo
2016-01-21

Abstract

Introduction 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. Matherials & Methods 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 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-gamma but only low levels of IL-10, indicating their ability to elicit a T(H)1-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 T(H)1 cytokines. Conclusion Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer.
Settore MED/04 - Patologia Generale
VISUALIZZAZIONE IN VIVO DELLA MIGRAZIONE DI CELLULE DENDRITICHE IN UN PROTOCOLLO VACCINALE IN UN MODELLO MURINO DI CARCINOMA MAMMARIO MEDIANTE RISONANZA MAGNETICA E IMAGING DELLA FLUORESCENZA.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/438965
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