Cytostatic Murine B16 Cell-pulsed Dendritic Cells Induce Effective Protection Against Melanoma in Mice

Abstract

Background: Peripheral blood mononuclear cells (PBMCs) present an antitumor activity in vitro on doxorubicin-resistant B16 melanoma (B16R) spheroids, but do not inhibit tumor growth in vivo. This study aimed to improve in vivo the antitumor immune response by using antigen presenting cells. Materials and Methods: After injection of B16R cells, mice received either tumor cell lysate-pulsed PBMCs, or naive or cytostatic tumor cell-pulsed bone marrow-derived dendritic cells (DCs). Tumor development and mouse survival were followed and spleen cell cytotoxic activity against B16R was estimated in vitro by Lactate dehydrogenase activity measurement. Results: The best results were obtained with peri-tumoral injections of cytostatic tumor cell-pulsed DCs which induced tumor regression, increased mouse survival and exhibited a higher splenocyte cytotoxic activity against B16R cells. When injected at a distant site, the efficacy was reduced. Furthermore, preventative injections of pulsed DCs induced protection of mice against B16R cells. Conclusion: These results show the important role of cytostatic tumor cell-pulsed DCs in a specific antitumor immunity establishment. Consequently, they could be used combined with other treatments to improve clinical outcomes.