Studies in a murine B16 melanoma model show that persistent antigen at vaccination sites induces CD8+ T cell sequestration, dysfunction and deletion

ABSTRACT: To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN-γ and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-p

ORGANISM(S): Mus musculus

SUBMITTER: Wencai Ma 

PROVIDER: E-GEOD-43929 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress