Transient Treg depletion enhances therapeutic anti-cancer vaccination

Immun Inflamm Dis. 2016 Nov 21;5(1):16-28. doi: 10.1002/iid3.136. eCollection 2017 Mar.


Introduction: Regulatory T cells (Treg) play an important role in suppressing anti- immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti-cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg.

Methods: Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored.

Results: DTX specifically depleted Treg in a transient, dose-dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor-peptide vaccination.

Conclusions: BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti-tumor immunity. DTX-mediated Treg depletion is transient, dose-dependent, and leads to strong anti-tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor-specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies.

Keywords: depletion; Cancer immunotherapy; regulatory T cell; tumor immunology; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / pharmacology*
  • Cell Line, Tumor
  • Diphtheria Toxin / pharmacology*
  • Epitopes
  • Forkhead Transcription Factors / genetics
  • Heparin-binding EGF-like Growth Factor / genetics
  • Immunotherapy
  • Lymphocyte Depletion*
  • Mice, Transgenic
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Peptides / pharmacology
  • T-Lymphocytes, Regulatory / immunology*
  • Vaccination


  • Cancer Vaccines
  • Diphtheria Toxin
  • Epitopes
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Peptides