Irradiated lactic acid-stimulated tumour cells promote the antitumour immunity as a therapeutic vaccine

Low pH and lactate accumulation are characteristic features of the tumour microenvironment. With our study finding that high concentrations of lactic acid can inhibit tumour growth, it is conceivable that the administration of lactic acid could promote antitumour immunity in the context of a tumour vaccine. To test this concept, we studied the antitumour effect of irradiated tumour cells stimulated with lactic acid in mouse xenograft models to potentially improve whole-cell tumour vaccines. In this study, we found that the effects of lactic acid-stimulated tumour cells on dendritic cells (DCs) included enhancing phagocytic function and stimulating maturation and aggregation. Moreover, lactic acid could potentiate the immunogenicity of an irradiated whole-tumour cell vaccine and thus inhibit tumour growth. We further verified that the antitumour immune response was mediated by CD8+ T cells. In addition, interferon-γ-expressing CD4+ and CD8+ T cell numbers increased in the spleen and lymph nodes of mice immunized with the irradiated lactic acid-stimulated cells. Furthermore, changes in the tumour microenvironment were also observed in this study. Our findings may be helpful for developing a new strategy for cancer therapy.