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Tumors need less regulation

Regulatory T cells (green) contact other T cells (red) to prevent effective tumor immunity. Zou/Macmillan

Efforts to induce anti-tumor immunity have so far proven disappointing. Now, Tyler Curiel, Weiping Zou (Tulane University, New Orleans, LA), and colleagues suggest that greater success may come if clinicians first disable regulatory T (T_reg) cells. These cells, say the group, are recruited by human tumors to damp down any immune response against tumor cells.

T_reg 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 T_reg 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 T_reg cells, with more T_reg cells present at later tumor stages. The patients also have fewer than normal T_reg cells in their lymph nodes—the normal home of the cells. In mice containing human tumor cells the T_reg accumulation in tumors is dependent on the chemokine CCL22, which is produced at high levels by macrophages in the tumors.

Transfer of T_reg cells to mice blocked the protective effects of tumor-specific effector T cells. And human patients with more T_reg cells had a poorer prognosis, even after controlling for tumor stage.

T_reg 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 T_reg cells. "You have to get rid of these suppressive mechanisms," he says, "and only then can you push the tumor-specific immunity."

Reference:

Curiel, T.J., et al. 2004. Nat. Med. doi: 10.1038/nm1093.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 851K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?