Myeloid-derived suppressor cells (MDSC) may represent a shared mechanism of the immune suppression that occurs during gestation and tumour growth, suggests the study of a mouse model of metastasis published in the Journal of Clinical Investigation.

Metastasis is a multistage process that requires cells to detach from the primary tumour mass, migrate towards and invade lymphatic or blood vessels, survive within the circulation, attach to the endothelium of distant organs, penetrate the endothelial barrier, and establish new tumour colonies. The process has been found to be highly inefficient, with estimates suggesting that less than 0.1% of tumour cells that penetrate the circulation end up forming metastatic colonies. One suggestion has been that immune surveillance may keep micro metastases in check.

Breast cells that arise during pregnancy have been shown to display early metastasis raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumour dissemination. In the current study Ivan Stamenkovic and colleagues, from the University of Lausanne (Switzerland), showed that when pregnant mice were injected with melanoma cells they developed a greater number of metastases than did their virgin counterparts.

When the investigators went on to compare the number of active NK cells in virgin and 16 day pregnant mice, they found decreased NK activity in the pregnant mice. They furthermore showed that MDSC levels rose during pregnancy and reached a peak around day 14, with NK levels starting to drop from day 6 of pregnancy. To determine the functional effect of MDSCs on metastasis the investigators depleted both pregnant and virgin mice of these cells using an antibody. The results showed that the volume of metastasis remained the same in the virgin mice but was reduced in the pregnant mice.

"In conclusion we postulate that the many previously reported similarities in molecular and cellular mechanisms involved in cancer progression and placentation should be extended to include a common mechanism for increasing permissiveness to metastasis in target organs by a process that involves, at least in part, accumulation of MDSCs and suppression of NK cell activity," wrote the authors.

Reference

L A Mauti, M Le Bitoux, K Baumer, et al. Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation, JCI Doi:10.1172/JCI41936, Published June 6, 2011