An immunosurveillance mechanism controls cancer cell ploidy

Science. 2012 Sep 28;337(6102):1678-84. doi: 10.1126/science.1224922.

Abstract

Cancer cells accommodate multiple genetic and epigenetic alterations that initially activate intrinsic (cell-autonomous) and extrinsic (immune-mediated) oncosuppressive mechanisms. Only once these barriers to oncogenesis have been overcome can malignant growth proceed unrestrained. Tetraploidization can contribute to oncogenesis because hyperploid cells are genomically unstable. We report that hyperploid cancer cells become immunogenic because of a constitutive endoplasmic reticulum stress response resulting in the aberrant cell surface exposure of calreticulin. Hyperploid, calreticulin-exposing cancer cells readily proliferated in immunodeficient mice and conserved their increased DNA content. In contrast, hyperploid cells injected into immunocompetent mice generated tumors only after a delay, and such tumors exhibited reduced DNA content, endoplasmic reticulum stress, and calreticulin exposure. Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calreticulin / immunology
  • Cell Line, Tumor
  • Common Variable Immunodeficiency / genetics
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • Endoplasmic Reticulum Stress / immunology*
  • Eukaryotic Initiation Factor-2 / metabolism
  • Humans
  • Immunocompetence
  • Immunologic Surveillance*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / chemically induced
  • Neoplasms / genetics*
  • Neoplasms / immunology*
  • Phosphorylation
  • Ploidies*

Substances

  • Calreticulin
  • DNA, Neoplasm
  • Eukaryotic Initiation Factor-2