Research ArticleCancer Immunotherapy

CD25 Blockade Depletes and Selectively Reprograms Regulatory T Cells in Concert with Immunotherapy in Cancer Patients

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Science Translational Medicine  16 May 2012:
Vol. 4, Issue 134, pp. 134ra62
DOI: 10.1126/scitranslmed.3003330

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Rehabilitating Tregs

In A Clockwork Orange, a young criminal undergoes a controversial rehabilitation therapy that reprograms him to become sick at even the thought of violence. Indeed, rehabilitation, although carried out with much less extreme measures, is a critical strategy for reforming many types of bad apples. Rech et al. now extend this concept to the delinquent regulatory T cells (Tregs) that suppress antitumor immune responses.

Tregs perform a critical role in healthy individuals—they prevent immune cells from the attacks on their host that causes autoimmunity. However, in the tumor microenvironment, Tregs are insidious—inhibiting immune responses against the tumor itself. Rech et al. hypothesized that daclizumab, a Food and Drug Administration–approved antibody to CD25, which is expressed on Tregs, could deplete Tregs and restore the antitumor immune response. They found in vitro that Tregs treated with daclizumab lost their suppressive function and secreted interferon-γ, which is consistent with reprogramming to effector T cells. They then treated patients with daclizumab in conjunction with an experimental vaccine for metastatic breast cancer. These patients had fewer Tregs and increased levels of vaccine antigen-specific effector T cell responses. Despite the loss of Tregs, these patients did not develop autoimmunity. Although these are still early studies, they provide hope that daclizumab may help to restore antitumor immunity without inducing autoimmunity.