An immunosurveillance mechanism controls cancer cell ploidy. Academic Article uri icon

Overview

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.

authors

  • Senovilla, Laura
  • Vitale, Ilio
  • Martins, Isabelle
  • Tailler, Maximilien
  • Pailleret, Claire
  • Michaud, Mickaël
  • Galluzzi, Lorenzo
  • Adjemian, Sandy
  • Kepp, Oliver
  • Niso-Santano, Mireia
  • Shen, Shensi
  • Mariño, Guillermo
  • Criollo, Alfredo
  • Boilève, Alice
  • Job, Bastien
  • Ladoire, Sylvain
  • Ghiringhelli, François
  • Sistigu, Antonella
  • Yamazaki, Takahiro
  • Rello-Varona, Santiago
  • Locher, Clara
  • Poirier-Colame, Vichnou
  • Talbot, Monique
  • Valent, Alexander
  • Berardinelli, Francesco
  • Antoccia, Antonio
  • Ciccosanti, Fabiola
  • Fimia, Gian Maria
  • Piacentini, Mauro
  • Fueyo, Antonio
  • Messina, Nicole L
  • Li, Ming
  • Chan, Christopher J
  • Sigl, Verena
  • Pourcher, Guillaume
  • Ruckenstuhl, Christoph
  • Carmona-Gutierrez, Didac
  • Lazar, Vladimir
  • Penninger, Josef M
  • Madeo, Frank
  • López-Otín, Carlos
  • Smyth, Mark J
  • Zitvogel, Laurence
  • Castedo, Maria
  • Kroemer, Guido

publication date

  • September 28, 2012

Research

keywords

  • Endoplasmic Reticulum Stress
  • Immunologic Surveillance
  • Neoplasms
  • Ploidies

Identity

PubMed ID

  • 23019653

Additional Document Info

volume

  • 337

issue

  • 6102