Abstract 4763: Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate: immunologic effects in mice bearing carcinogen-induced premalignant oral lesions

Abstract

Abstract Most studies with dendritic cell vaccines have focused on eliminating or preventing the progression of already established malignancies. This is complicated by the immune suppression that is 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 dendritic cell vaccine during the premalignant stages of oral squamous cell carcinoma (OSCC), prior to the development of systemic immune suppression. Mice treated with the carcinogen 4-nitroquinoline-1-oxide (4NQO) in drinking water develop premalignant oral lesions which subsequently progress to OSCC. As previous studies in our lab demonstrated that premalignant lesions and OSCC share overexpression of common tumor antigens, bone-marrow derived dendritic cells were pulsed with premalignant lesion lysate and administered to 4NQO-treated C57/BL6 mice exhibiting premalignant lesions. Immunohistochemical analysis demonstrated a similar increase in the number of CD8+ and CD4+ cells in the tongues of both the 4NQO-treated mice immunized with premalignant lesion-pulsed dendritic cells (DCpm) and the 4NQO-treated mice immunized with keratinocyte-pulsed dendritic cells (DCker) compared to 4NQO-treated mice injected with saline. However, the tongues of 4NQO-treated DCpm mice exhibited a dramatic decrease in the number of Foxp3+ cells compared to both 4NQO-treated control groups. In addition, splenocytes from 4NQO-treated DCpm mice released greater amounts of both IFN-γ and IL-2 in response to challenge with premalignant lysate compared to splenocytes from 4NQO-treated DCker mice in response to challenge with keratinocyte lysate. These studies indicate that stimulated dendritic cells, regardless of pulsing with premalignant lesions or keratinocytes, may be able to elicit an upregulation of T cells in the tongue. However, DCpm immunization specifically appears to result in a decrease in immune inhibitory regulatory T cells in the tongue and an increase in splenocyte secretion of immune stimulatory cytokines in response to antigenic challenge. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4763.