Polyploid cells – those with more than two sets of chromosomes – are normally eliminated by cell-autonomous mechanisms; when this mechanism fails, cancer can develop. Senovilla et al. now report that there is an additional, non-cell-autonomous mechanism that eliminates polyploid cells. They found that cells with four or more sets of chromosomes have increased levels of endoplasmic reticulum stress, which leads to cell-surface exposure of calreticulin (CRT). The authors went on to show that CRT cell-surface exposure stimulates immunosurveillance: when injected into immunocompetent (but not immunodeficient) mice, hyperploid CT26 colon cancer cells induced cancer more readily than euploid CT26 cells. This effect was not observed if CRT was depleted from hyperploid cells before injection. CRT was found to be important for T-cell-mediated immunoselection against polyploid cells in the adoptive transfer experiments, as well as in chemically or genetically induced cancer in mice. Finally, the authors show that breast cancer patients who responded well to therapy had residual carcinoma cells with smaller nuclei, and showed a greater local immune response, compared with nonresponders. These results shed light on a previously unappreciated cancer immunosurveillance mechanism.
- Written by editorial staff. © 2012. Published by The Company of Biologists Ltd.
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