Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy

PLoS One. 2016 Jan 21;11(1):e0146622. doi: 10.1371/journal.pone.0146622. eCollection 2016.

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-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.

Conclusion: Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Female
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class II / biosynthesis
  • Immunotherapy / methods*
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-12 / biosynthesis
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells / immunology
  • Tissue Extracts / pharmacology*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • IL10 protein, mouse
  • Tissue Extracts
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma

Grants and funding

This work was supported by PRIN 2008 (Progetti di Rilevante Interesse Nazionale, Health Ministry, project no. 20082NHWH9_001) received by MC and AIRC (Associazione Italiana per la Ricerca sul Cancro; funded project n° IG-9311) received by MC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.