Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity

Cancer Res. 2010 Feb 1;70(3):855-8. doi: 10.1158/0008-5472.CAN-09-3566. Epub 2010 Jan 19.

Abstract

By destroying tumor cells, conventional anticancer therapies may stimulate the host immune system to eliminate residual disease. Anthracyclines, oxaliplatin, and ionizing irradiation activate a type of tumor cell death that elicits efficient anticancer immune responses depending on interferon gamma (IFNgamma) and the IFNgamma receptor. Thus, dying tumor cells emit danger signals that are perceived by dendritic cells (DC), which link innate and cognate immune responses. Recently, we observed that ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1beta (IL-1beta). IL-1beta then is required for the adequate polarization of IFNgamma-producing CD8(+) T cells. These results imply a novel danger signal, ATP, and a novel receptor, P2RX7, in the chemotherapy-elicited anticancer immune response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cell Death / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Immunity / immunology*
  • Interferon gamma Receptor
  • Interferon-gamma / metabolism
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Receptors, Interferon / metabolism
  • Signal Transduction / immunology

Substances

  • Receptors, Interferon
  • Interferon-gamma
  • Adenosine Triphosphate