Altering regulatory T cell function in cancer immunotherapy: A novel means to boost the efficacy of cancer vaccines

Jens Ruter, Brian G. Barnett, Ilona Kryczek, Michael J. Brumlik, Benjamin J. Daniel, George Coukos, Weiping Zou, Tyler J. Curiel

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1761-1770
Number of pages10
JournalFrontiers in Bioscience
Volume14
Issue number5
DOIs
StatePublished - Jan 1 2009

Keywords

  • Immune suppression
  • Immunopathology
  • Immunotherapy
  • Ontak
  • Review
  • T cell
  • T regulatory cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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