An immunosurveillance mechanism controls cancer cell ploidy - PubMed (original) (raw)

. 2012 Sep 28;337(6102):1678-84.

doi: 10.1126/science.1224922.

Ilio Vitale, Isabelle Martins, Maximilien Tailler, Claire Pailleret, Mickaël Michaud, Lorenzo Galluzzi, Sandy Adjemian, Oliver Kepp, Mireia Niso-Santano, Shensi Shen, Guillermo Mariño, Alfredo Criollo, Alice Boilève, Bastien Job, Sylvain Ladoire, François Ghiringhelli, Antonella Sistigu, Takahiro Yamazaki, Santiago Rello-Varona, Clara 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

Affiliations

• PMID: 23019653
• DOI: 10.1126/science.1224922

An immunosurveillance mechanism controls cancer cell ploidy

Laura Senovilla et al. Science. 2012.

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.

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Comment in

• Cancer. Immune surveillance from chromosomal chaos?
  Zanetti M, Mahadevan NR. Zanetti M, et al. Science. 2012 Sep 28;337(6102):1616-7. doi: 10.1126/science.1228464. Science. 2012. PMID: 23019639 No abstract available.
• Tumour immunology: chromosome overload.
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• A four-lane highway to cancer.
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