Open Access
Altering regulatory T cell function in cancer immunotherapy: a novel means to boost the efficacy of cancer vaccines
Jens Ruter1,Brian G Barnett1,Ilona Kryczek1,Michael J Brumlik1,Benjamin J Daniel1,George Coukos1,Weiping Zou1,Tyler J Curiel1
Department of Medicine, Hematology and Medical Oncology, Tulane University School of Medicine, 1430 Tulane Avenue SL-78, New Orleans, LA 70112, USA
DOI: 10.2741/3338 Volume 14 Issue 5, pp.1761-1770
Published: 01 January 2009

Cancers express tumor associated antigens that should elicit immune attack, but spontaneous immune rejection of established cancer is rare. Recent data demonstrate that specific and active tumor-mediated mechanisms hinder host anti-tumor immunity. CD4+CD25+ T regulatory cells (Tregs) are important mediators of active immune evasion in cancer. Disrupting tumor-mediated mechanisms hindering host immunity is a novel approach to tumor immunotherapy. Treg depletion improves endogenous anti-tumor immunity and the efficacy of active immunotherapy in animal models for cancer, suggesting that inhibiting Treg function could also improve the limited successes of human cancer immunotherapy. We have identified five strategies to block Treg activity: depletion, interference with trafficking, inhibition of differentiation, blockade of function or raising the effector T cell threshold for suppression. Discovery of additional regulatory cell populations expands the potential targets for these approaches. The fusion toxin denileukin diftitox (Ontak) reduces Treg numbers and function in the blood of some patients with cancer. We discuss specific strategies to block Treg activity and present some of our preliminary data in this area. Combining Treg depletion with active vaccination and other approaches poses additional challenges that are discussed.

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Jens Ruter, Brian G Barnett, Ilona Kryczek, Michael J Brumlik, Benjamin J Daniel, George Coukos, Weiping Zou, Tyler J Curiel. Altering regulatory T cell function in cancer immunotherapy: a novel means to boost the efficacy of cancer vaccines. Frontiers in Bioscience-Landmark. 2009. 14(5); 1761-1770.