Dendritic cell immunotherapy has its antitumor action improved by the LPS in the maturation process.

Abstract

Immunotherapy with dendritic cells (DCs) in cancer patients aims to activate the immune response to eliminate neoplastic cells. The present study aimed to investigate lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells in investigating antitumor immune response in experimental breast cancer. For this, we submitted bone marrow pluripotent cells of Balb/c mice differentiated by GM-CSF and IL-4 to maturation with TNF-α and tumor lysate (DCs protocol) or with TNF-α, LPS, and tumor lysate (LPS/DCs protocol). Both immunotherapies were tested in 4T1 breast cancer to evaluate their impact on splenic and tumor microenvironment. We observed that DCs and LPS/DCs reduce the tumor growth rate (p < 0.0001). Besides, the LPS/DCs vaccine shows higher splenic and intratumoral T helper lymphocytes (p < 0.001). Both vaccines increased the production of IFN-γ in the tumor microenvironment (p < 0.0001). The LPS/DCs induced lower Treg lymphocytes and macrophages in the tumor microenvironment (p < 0.0001). The results allow us to conclude that bone marrow-derived dendritic cells stimulated with LPS have been shown to reduce tumor growth rate efficiently and could be better immunotherapy in breast cancer by reducing immunosuppressive cells and increasing antitumoral immune cells in the tumor microenvironment.