Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate results in an increase in CD4+ and CD8+ T cells and a decrease in Foxp3+ cells in tongues of mice bearing carcinogen-induced premalignant oral lesions. (131.24)

Abstract

Most studies with dendritic cell vaccines have focused on eliminating or preventing progression of established malignancies. This is complicated by the immune suppression often exhibited in the presence of solid carcinomas. The goal of this study is to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of oral squamous cell carcinoma, prior to development of systemic immune suppression. Mice treated with the carcinogen 4NQO in drinking water develop premalignant oral lesions which progress to OSCC. As previous studies in our lab demonstrated that premalignant lesions and OSCC overexpress common tumor antigens, BM-derived DCs were pulsed with premalignant lesion lysate and administered to 4NQO-treated C57/BL6 mice exhibiting premalignant lesions. Immunohistochemical analysis demonstrated an increase in CD8+ and CD4+ cells, as well as a decrease in Foxp3+ cells, in the tongues of 4NQO-treated mice immunized with premalignant lesion-pulsed dendritic cells (DCpm) compared to 4NQO-treated control mice. In addition, splenocytes from 4NQO-treated DCpm mice released greater amounts of IFN-γ compared to splenocytes from 4NQO-treated control mice in response to stimulation with antigen. These studies indicate that DCpm vaccination may be able to elicit a stimulatory immune response in 4NQO-treated mice bearing premalignant lesions.