Immunotherapy with dendritic cells in an animal model of early pulmonary metastatic squamous cell carcinoma.

Abstract

Distant metastases is becoming a more frequently recognized pattern of treatment failure in patients with squamous cell carcinoma of the head and neck (SCCHN). In this study, we evaluated the effect of a dendritic cell (DC)-based vaccine in an early pulmonary metastatic murine model with the aim of providing an effective treatment for SCCHN patients presenting with occult pulmonary metastasis. In vivo animal experiments were conducted in C3H/He immunocompetent mice using the SCCVII syngeneic squamous carcinoma cell line. SCCVII cells were injected through the tail vein to establish early pulmonary metastases. Bone marrow-derived DCs were cultured and educated with ultraviolet B-irradiated apoptotic SCCVII cells before adoptive transfer into the inguinal area. Control groups were vaccinated with normal saline, naïve DCs, or apoptotic tumor cells. In the apoptotic SCCVII-pulsed DC group, the number of pulmonary tumor nodules was reduced, extirpated lung weight was less, and survival was longer than in control groups. Differences were statistically significant (P < .0001). Specific antitumor immunity was established only in the pulsed DC group, which was confirmed by an interferon-γ enzyme-linked immunosorbent assay. In an early pulmonary metastatic SCC murine model, systemic antitumor responses can be elicited by adoptive transfers of DCs, which were primed with apoptotic tumor cells. We hope this study will help improve overall survival of patients with SCCHN, especially when they have early or occult pulmonary metastasis.