CD11c+ MHCIIlo GM-CSF-bone marrow-derived dendritic cells act as antigen donor cells and as antigen presenting cells in neoepitope-elicited tumor immunity against a mouse fibrosarcoma

Abstract

Dendritic cells play a critical role in initiating T-cell responses. In spite of this recognition, they have not been used widely as adjuvants, nor is the mechanism of their adjuvanticity fully understood. Here, using a mutated neoepitope of a mouse fibrosarcoma as the antigen, and tumor rejection as the end point, we show that dendritic cells but not macrophages possess superior adjuvanticity. Several types of dendritic cells, such as bone marrow-derived dendritic cells (GM-CSF cultured or FLT3-ligand induced) or monocyte-derived ones, are powerful adjuvants, although GM-CSF-cultured cells show the highest activity. Among these, the CD11c+ MHCIIlo sub-set, distinguishable by a distinct transcriptional profile including a higher expression of heat shock protein receptors CD91 and LOX1, mannose receptors and TLRs, is significantly superior to the CD11c+ MHCIIhi sub-set. Finally, dendritic cells exert their adjuvanticity by acting as both antigen donor cells (i.e., antigen reservoirs) as well as antigen presenting cells.Electronic supplementary materialThe online version of this article (10.1007/s00262-018-2202-4) contains supplementary material, which is available to authorized users.

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“…The 8 MS-defined neoepitopes were used to immunize naive BALB/cJ mice twice, 1 week apart, with neoepitope-pulsed bone marrow–derived dendritic cells (BMDCs, 3 × 10 6 ) as adjuvants, as previously published (22). All mice were challenged with 95,000 Meth A tumor cells 1 week after the second immunization, and tumor growth was monitored in individual mice (Figure 2, A and B).…”

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