An indiscriminate increase in cellular DNA content (hyperploidy) is an important contributor to oncogenesis because of its genome-destabilizing effects. In Science, Kroemer et al. identify a mechanism whereby the immune system recognizes and controls hyperploid cells. Cytotoxic agents can elicit immunogenic tumor killing, but this requires an endoplasmic reticulum stress response that translocates calreticulin to the plasma membrane. The authors find that hyperploidy also correlates closely with the translocation of calreticulin. Hyperploid tumors grafted to immunocompetent mice are destroyed by the immune system, but this depends on the surface expression of calreticulin. Finally, patients with breast cancer that responds to cytotoxic drugs have a lower DNA content than do unresponsive patients, which suggests that the tumors are immunoselected by the rejection of calreticulin-positive hyperploid cells. The immune system can therefore detect an important cellular property associated with cancerous transformation through the expression of calreticulin on target cells.

Science 337, 1678–1684 (2012)