Interleukin-2 induces proliferation of regulatory T cells in patients with ovarian cancer

Wei S et al. (2007) Interleukin-2 administration alters the CD4+FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res 67: 7487–7494

Interleukin (IL)-2 immunotherapy results in a 16–20% objective response rate in selected patients with cancer. Studies have demonstrated that IL-2 administration increases the pool of regulatory T (T_REG) cells in patients with pediatric sarcoma, melanoma and renal cell carcinoma. Wei et al. examined the effect of IL-2 therapy on T_REG cells in patients with ovarian cancer.

The study included 31 patients with ovarian cancer treated weekly with IL-2 for 16 weeks. IL-2 induced the proliferation of CD4⁺FOXP3⁺ T_REG cells in vitro in a dose-dependent manner. The administration of IL-2 induced the proliferation of existent FOXP3⁺ cells. The prevalence of FOXP3⁺ T_REG cells before IL-2 administration was negatively correlated with the potency of IL-2-induced proliferation, suggesting that T_REG cells are a key factor in the regulation of self-proliferation. In vivo, IL-2 increased the percentages of CD4⁺CD25^high T cells and induced their proliferation. These CD4⁺CD25^high T cells were also FOXP3⁺ and could suppress T-cell activation. IL-2 upregulated the expression of the chemokine receptors CCR4 and CXCR4 on T_REG cells, which might enable their migration in response to CCL22 and CXCL12 (the ligands for CCR4 and CXCR4, respectively) in the tumor microenvironment. At 3 weeks after IL-2 treatment cessation, the number of T_REG cells was significantly reduced in clinical responders compared with nonresponders, indicating that T_REG cell changes might predict response after therapy.

On the basis of these results, the authors conclude that IL-2 induces the proliferation of T_REG cells and may promote T_REG-cell migration in patients with ovarian cancer.