Adjuvants that improve the ratio of antigen-specific effector to regulatory T cells enhance tumor immunity

Cancer Res. 2013 Nov 15;73(22):6597-608. doi: 10.1158/0008-5472.CAN-13-0875. Epub 2013 Sep 18.


Antitumor immunity is strongly influenced by the balance of tumor antigen-specific effector T cells (Teff) and regulatory T cells (Treg). However, the impact that vaccine adjuvants have in regulating the balance of antigen-specific T-cell populations is not well understood. We found that antigen-specific Tregs were induced following subcutaneous vaccination with either OVA or melanoma-derived peptides, with a restricted expansion of Teffs. Addition of the adjuvants CpG-ODN or Poly(I:C) preferentially amplified Teffs over Tregs, dramatically increasing the antigen-specific Teff:Treg ratios and inducing polyfunctional effector cells. In contrast, two other adjuvants, imiquimod and Quil A saponin, favored an expansion of antigen-specific Tregs and failed to increase Teff:Treg ratios. Following therapeutic vaccination of tumor-bearing mice, high ratios of tumor-specific Teffs:Tregs in draining lymph nodes were associated with enhanced CD8(+) T-cell infiltration at the tumor site and a durable rejection of tumors. Vaccine formulations of peptide+CpG-ODN or Poly(I:C) induced selective production of proinflammatory type I cytokines early after vaccination. This environment promoted CD8(+) and CD4(+) Teff expansion over that of antigen-specific Tregs, tipping the Teff to Treg balance to favor effector cells. Our findings advance understanding of the influence of different adjuvants on T-cell populations, facilitating the rational design of more effective cancer vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antigens / immunology
  • Cancer Vaccines / administration & dosage
  • Female
  • Immunity, Cellular / drug effects*
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • T-Cell Antigen Receptor Specificity / drug effects*
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / pathology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Treatment Outcome
  • Tumor Cells, Cultured


  • Adjuvants, Immunologic
  • Antigens
  • Cancer Vaccines