Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate stimulates Th1 and Th17 immunity in mice bearing carcinogen-induced premalignant oral lesions. (165.13)

Abstract

Abstract The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by the immune suppression often exhibited in the presence of solid carcinomas such as head and neck squamous cell carcinoma (HNSCC). 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 HNSCC, prior to development of immune suppression. Mice treated with the carcinogen 4NQO in drinking water develop premalignant oral lesions which progress to HNSCC. As previous studies demonstrated that premalignant lesions and HNSCC overexpress common tumor antigens, BM-derived DCs were pulsed with premalignant lesion lysate (DCpm) and administered to 4NQO-treated mice exhibiting premalignant lesions. Lymphocytes were then isolated and tested for response to antigenic challenge. The levels of Th1, Th17, and to a lesser extent, Th2 cytokines, were increased in supernatant of unchallenged lymphocytes from DCpm-vaccinated mice compared to controls. In response to premalignant and HNSCC challenge, lymphocytes from DCpm-vaccinated mice released greatly increased levels of Th1 cytokines than control lymphocytes, while levels of Th2 cytokines released by control lymphocytes increased to, or near to, levels released from DCpm-vaccinated mouse lymphocytes. This suggests that DCpm vaccination of 4NQO-treated mice stimulates the development of Th1 immunity that may be specific to premalignant and HNSCC antigens.