An Immunosurveillance Mechanism Controls Cancer Cell Ploidy

作者：Senovilla Laura; Vitale Ilio; Martins Isabelle; Tailler Maximilien; Pailleret Claire; Michaud Mickael; Galluzzi Lorenzo; Adjemian Sandy; Kepp Oliver; Niso Santano Mireia; Shen Shensi; Marino Guillermo; Criollo Alfredo; Boileve Alice; Job Bastien; Ladoire Sylvain; Ghiringhelli Francois; Sistigu Antonella; Yamazaki Takahiro; Rello Varona Santiago; Locher Clara; Poirier Colame Vichnou; Talbot Monique; Valent Alexander; Berardinelli Francesco; Antoccia Antonio

来源：Science, 2012, 337(6102): 1678-1684.

DOI：10.1126/science.1224922

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.

• 出版日期2012-9-28