An immunosurveillance mechanism controls cancer cell ploidy

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1678-1684
Number of pages7
JournalScience
Volume337
Issue number6102
DOIs
Publication statusPublished - Sep 28 2012

ASJC Scopus subject areas

  • General

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