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


Autoria(s): Perret R.; Sierro S.; Botelho N.K.; Corgnac S.; Donda A.; Romero P.
Data(s)

2013

Resumo

Antitumor immunity is strongly influenced by the balance of tumor antigen-specific effector and regulatory T cells. 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 T regulatory cells (Treg) were induced following subcutaneous vaccination with either OVA or melanoma-derived peptides, with a restricted expansion of effector T cells. Addition of the adjuvants CpG-ODN or Poly(I:C) preferentially amplified effector T cells over Tregs, dramatically increasing the antigen-specific T effector: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 effector T cell:Treg ratios. Following therapeutic vaccination of tumor-bearing mice, high ratios of tumor-specific effector T cells: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 pro-inflammatory Type I cytokines early after vaccination. This environment promoted CD8+ and CD4+ effector T cell expansion over that of antigen-specific Tregs, tipping the effector T cell 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.

Identificador

http://serval.unil.ch/?id=serval:BIB_C759116734DC

isbn:1538-7445 (Electronic)

pmid:24048821

doi:10.1158/0008-5472.CAN-13-0875

isiid:000327321700007

Idioma(s)

en

Fonte

Cancer Research, vol. 73, no. 22, pp. 6597-608

Tipo

info:eu-repo/semantics/article

article