Monocyte-derived dendritic cells are critical for the induction of anti-tumor immune responses (TUM4P.932)

Abstract

Abstract The DC subsets that are required for the induction of effective anti-tumor immune responses and the success of immunotherapy are unknown. We used mouse models to compare different immune-activating agents for their impact on tumor growth, tumor-specific T cells, cytokine production and DC activation. Treatments with poly I:C or a combination of monososdium-urate crystals (MSU) + Mycobacterium smegmatis delayed growth of B16 melanoma and 4T1 mammary carcinoma tumors, whereas LPS, M. smegmatis or MSU alone were ineffective. Effective treatments required both CD8+ and NK1.1+ cells, and increased CD8+ T cell priming, tumor-infiltration by effector cells and effector cytokine production. In addition, only the successful treatments induced the appearance of a population of monocyte-derived DC in tumor-draining lymph nodes. Recent experiments revealed that immunotherapy was required for the differentiation of blood monocytes into DC in the lymph node, and that these monocyte-derived DC were both necessary and sufficient for successful immunotherapy of B16 melanoma tumors. Further experiments are required to clarify the precise function of this DC population. We conclude that the activation of existing DC subsets is not sufficient for the induction of anti-tumor immunity, whereas newly recruited inflammatory DC are critical mediators of the successful activation of anti-tumour immune responses.