Medical University of South Carolina Charleston United States
Lung cancer disproportionately affects United States Veterans with rates of disease nearly double to those found in the general population. Immunosurveillance, whereby an effective immune response can detect and eliminate abnormal cells before they progress to invasive malignancy, provides rationale for the development of a prophylactic vaccination regimen. Herein, we developed an adenoviral-based vaccination delivering MUC1tumor-associated antigen and the immuno stimulatory molecule ICOS-L to induce a unique subset of effector Tcells, IL-17-producing CD4 T cells, termed Th17s, shown to have superior antitumor reactivity. As peripheral tolerance limits the induction of immunity to self-derived tumor antigens, we have examined the ability to enhance vaccine immunogenicity through the ablation of regulatory T cells Tregs prior to immunization. We have illustrated that ICOS-L augmented vaccination significantly enhances Th17, but not Tc17 immune responses against MUC1. We further demonstrate that ablation of Tregs prior to immunization increases both cellular and humoral vaccine-induced immunity against MUC1. Preventative vaccination significantly enhanced protection against pulmonary tumor colonization with LLC-MUC1-Luc cells. Additional transcriptional profiling of tumorinfiltratingMUC1-reactive T cells is currently ongoing. Collectively, these studies represent a novel strategy for the prevention of lung cancer and will inform the design and optimization of next generation vaccine technology.