Treg cells have been studied primarily for their ability to turn off immune responses during organ transplantation or autoimmune disease. Preliminary results in mice suggested that depletion of Treg cells might improve tumor prognosis, although these experiments may have depleted other cell types.
Now, Zou's team finds that human malignant ovarian cancers contain substantial numbers of Treg cells, with more Treg cells present at later tumor stages. The patients also have fewer than normal Treg cells in their lymph nodes—the normal home of the cells. In mice containing human tumor cells the Treg accumulation in tumors is dependent on the chemokine CCL22, which is produced at high levels by macrophages in the tumors.
Transfer of Treg cells to mice blocked the protective effects of tumor-specific effector T cells. And human patients with more Treg cells had a poorer prognosis, even after controlling for tumor stage.
Treg cells probably function primarily in switching off an immune response so that it does not get out of control. Tumors appear to have coopted this mechanism to create a privileged environment for themselves. Zou is now pursuing a clinical trial to disable Treg cells. “You have to get rid of these suppressive mechanisms,” he says, “and only then can you push the tumor-specific immunity.” ▪