Shikonin induces immunogenic cell death in tumor cells and enhances dendritic cell-based cancer vaccine

Cancer Immunol Immunother. 2012 Nov;61(11):1989-2002. doi: 10.1007/s00262-012-1258-9. Epub 2012 Apr 19.

Abstract

Immunogenic cell death is characterized by damage-associated molecular patterns, which can enhance the maturation and antigen uptake of dendritic cells. Shikonin, an anti-inflammatory and antitumor phytochemical, was exploited here as an adjuvant for dendritic cell-based cancer vaccines via induction of immunogenic cell death. Shikonin can effectively activate both receptor- and mitochondria-mediated apoptosis and increase the expression of all five tested damage-associated molecular patterns in the resultant tumor cell lysates. The combination treatment with damage-associated molecular patterns and LPS activates dendritic cells to a high maturation status and enhances the priming of Th1/Th17 effector cells. Shikonin-tumor cell lysate-loaded mature dendritic cells exhibit a high level of CD86 and MHC class II and activate Th1 cells. The shikonin-tumor cell lysate-loaded dendritic cell vaccines result in a strong induction of cytotoxic activity of splenocytes against target tumor cells, a retardation in tumor growth, and an increase in the survival of test mice. The much enhanced immunogenicity and efficacy of the current cancer vaccine formulation, that is, the use of shikonin-treated tumor cells as cell lysates for the pulse of dendritic cells in culture, may suggest a new ex vivo approach for developing individualized, dendritic cells-based anticancer vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / immunology
  • B7-2 Antigen / immunology
  • Cancer Vaccines / therapeutic use*
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Genes, MHC Class II / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Naphthoquinones / administration & dosage*
  • Skin Neoplasms / therapy*
  • Spleen / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology

Substances

  • B7-2 Antigen
  • Cancer Vaccines
  • Cd86 protein, mouse
  • Naphthoquinones
  • shikonin