Poly(I:C)-induced tumour cell death leads to DC maturation and Th1 activation

Cancer Immunol Immunother. 2011 Nov;60(11):1609-24. doi: 10.1007/s00262-011-1058-7. Epub 2011 Jun 21.

Abstract

Dendritic cells (DCs) have the ability to generate peptide epitopes for MHC class I molecules derived from apoptotic tumour cells for direct recognition by cytotoxic T cells. This function has lead to DCs being used in vaccine strategies. In this study, we investigate the effect of inducing apoptosis in tumour cell lines using IFN-γ and poly(I:C), the subsequent maturation of the endocytosing DC and its ability to direct the resulting T cell response. We show that uptake of poly(I:C)-induced apoptotic tumour cells leads to DC maturation and activation with a Th1 cell polarising capacity. In contrast, these effects are not seen by DCs loaded with γ-irradiated apoptotic tumour cells. We propose that the manner in which tumour cells are induced to die can have a profound effect on the endocytosing DC and the resulting T cell response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology
  • Cell Death / immunology
  • Cell Line, Tumor
  • Cytokines / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Humans
  • Major Histocompatibility Complex / immunology
  • Melanoma / immunology*
  • Melanoma / pathology
  • Poly I-C / immunology
  • Poly I-C / pharmacology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Th1 Cells / immunology*

Substances

  • Cytokines
  • Poly I-C