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CD4⁺CD25⁺ Regulatory Lymphocytes Induce Regression of Intestinal Tumors in Apc^Min/+ Mice

Division of ¹ Comparative Medicine and ² Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts

Requests for reprints: Susan E. Erdman, Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139. Phone: 617-252-1804; Fax: 617-258-5708; E-mail: serdman{at}mit.edu.

Colorectal cancer in humans results from sequential genetic changes in intestinal epithelia commencing with inactivation of the APC tumor suppressor gene. Roles for host immunity in epithelial tumorigenesis are poorly understood. It has been previously shown that CD4⁺CD25⁺ lymphocytes inhibit colitis-associated epithelial tumors in Rag-deficient mice. Here we show that addition of CD4⁺CD25⁺ lymphocytes in Apc^Min/+ mice reduces multiplicity of epithelial adenomas. Interleukin-10 was required in regulatory cells for therapeutic effect. Recipients of regulatory cells showed increased apoptosis and down-regulation of cyclooxygenase-2 within tumors coincident with tumor regression. These data suggest a role for regulatory lymphocytes in epithelial homeostasis in the Apc^Min/+ mouse model of intestinal polyposis. Similarities with cancer of the breast, prostate, lung, and other sites raise the possibility of broader roles for regulatory lymphocytes in prevention and treatment of epithelial cancers in humans.

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