Melanoma Stem Cell Vaccine Modified with IL-33 Induces Anti-Tumor Immunity by Activating CD8+T Cells

Background: Melanoma stem cells (MSCs)-based vaccine strategies have been a potent immunotherapeutic approach for melanoma treatment, which aimed at inducing specific anti-tumor immunity and targeting cancer stem-like cells. To boost anti-melanoma activity induced by B16F10 CD44+CD133+ MSCs (B16F10 MSCs) vaccine, we generated a novel vaccine expressing IL-33. Tumor growth and pulmonary metastasis were assessed to estimate the effectiveness of the vaccine. Methods: The antitumor effect of the vaccine was observed in this study. The mechanism of inducing anti-tumor immunity was detected by flow cytometric assays, cytotoxicity assays, and ELISA, including expression of CD8+T cells surface and intracellular molecules, the cytotoxic activity of splenocytes in the immunized mice and secretion of serum cytokines.Results: We found that MSCs vaccine expressing IL-33 significantly inhibited melanoma growth and reduced the lung melanoma nodules. Mechanistic investigations established that the vaccine-primed CD8+T cells could selectively target MSCs and confer anti-tumor immunity, which included promoting the proliferation of CD8+T cells, inhibiting the differentiated depletion of CD8+T cells in vivo, inducing the formation of memory CD8+T cells, and activating specific cytotoxic T lymphocyte (CTL) immune response. Conclusions: MSCs vaccine expressing IL-33 is able to initiate anti-tumor specific immune response by activating CD8+T cells.