ICOSL-augmented adenoviral-based vaccination induces a bipolar Th17/Th1 T cell response against unglycosylated MUC1 antigen.

ICOSL-augmented adenoviral-based vaccination induces a bipolar Th17/Th1 T cell response against unglycosylated MUC1 antigen. Vaccine. 2018 Sep 12;: Authors: Carrell RK, Stanton RA, Ethier SP, LaRue AC, Soloff AC Abstract Cellular immunity established via immunotherapy holds the potential to eliminate solid tumors. Yet, cancer vaccines have failed to induce tumor-reactive T cells of sufficient quality to control disease. The inducible T cell costimulator (ICOS) pathway has been implicated in both the selective induction of immunity over tolerance as well as licensing of IL-17-polarized cellular immunity. Herein, we evaluated the ability of ICOS ligand (ICOSL) to augment the immunogenicity of adenoviral-based vaccination targeting the unglycosylated MUC1 peptide antigen. Vaccination disrupted immunotolerance in a transgenic mouse model recognizing human MUC1 as a self-antigen, inducing robust MUC1-specific immunity. Augmenting vaccination with ICOSL induced a bipolar Th17/Th1 effector profile, marked by increased MUC1-specific IL-17A production and RORγt expression in CD4+ but not CD8+ T cells which predominantly expressed IFNγ/IL-2 and T-bet. The polarization and maintenance of Th17 cells established following ICOSL augmented vaccination was highly durable, with elevated IL-17A and RORγt levels detected in CD4+ T cells up to 10 months after initial immunization. Furthermore, provision of ICOSL significantly enhanced MUC1-specific...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research