TY - JOUR AB - 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. AU - Senovilla, Laura AU - Vitale, Ilio AU - Martins, Isabelle AU - Tailler, Maximilien AU - Pailleret, Claire AU - Michaud, Mickaël AU - Galluzzi, Lorenzo AU - Adjemian, Sandy AU - Kepp, Oliver AU - Niso-Santano, Mireia AU - Shen, Shensi AU - Mariño, Guillermo AU - Criollo, Alfredo AU - Boilève, Alice AU - Job, Bastien AU - Ladoire, Sylvain AU - Ghiringhelli, François AU - Sistigu, Antonella AU - Yamazaki, Takahiro AU - Rello-Varona, Santiago AU - Locher, Clara AU - Poirier-Colame, Vichnou AU - Talbot, Monique AU - Valent, Alexander AU - Berardinelli, Francesco AU - Antoccia, Antonio AU - Ciccosanti, Fabiola AU - Fimia, Gian AU - Piacentini, Mauro AU - Fueyo, Antonio AU - Messina, Nicole AU - Li, Ming AU - Chan, Christopher AU - Sigl, Verena AU - Pourcher, Guillaume AU - Ruckenstuhl, Christoph AU - Carmona-Gutierrez, Didac AU - Lazar, Vladimir AU - Penninger, Josef AU - Madeo, Frank AU - López-Otín, Carlos AU - Smyth, Mark AU - Zitvogel, Laurence AU - Castedo, Maria AU - Kroemer, Guido C3 - 23019653 DA - 2012/09/28/ DO - 10.1126/science.1224922 ET - 2017/09/12/ IS - 6102 JF - Science PY - 2012 SE - 2012/09/28/ SP - 1678-84 TI - An immunosurveillance mechanism controls cancer cell ploidy. VL - 337 ER -