Investigating the use of antigen-presenting cells (APCs) as adjuvants, Ebrahimi-Nik et al. found that neoantigen-pulsed bone marrow-derived dendritic cells (BMDCs) differentiated with either GM-CSF or FLT3L, and monocyte-derived dendritic cells (but not macrophages) acted as strong in vivo adjuvants. Within GM-CSF-BMDCs, the CD11c+MHCIIlo subset had superior adjuvanticity and antigen uptake capacity compared to the more mature CD11c+MHCIIhi subset. The adjuvanticity of DCs could be attributed mainly to their roles as “antigen reservoirs” (i.e. - serving as antigen donors to other APCs), though they also contributed directly as APCs.
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(+) MHCII(lo) 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(+) MHCII(hi) 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.
Author Info: (1) Department of Immunology, School of Medicine, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut, 263 Farmington Ave, Farmington, CT, 06030-1601, USA. (
Author Info: (1) Department of Immunology, School of Medicine, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut, 263 Farmington Ave, Farmington, CT, 06030-1601, USA. (2) Department of Immunology, School of Medicine, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut, 263 Farmington Ave, Farmington, CT, 06030-1601, USA. (3) Department of Immunology, School of Medicine, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut, 263 Farmington Ave, Farmington, CT, 06030-1601, USA. (4) Department of Immunology, School of Medicine, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut, 263 Farmington Ave, Farmington, CT, 06030-1601, USA. (5) Department of Computer Science and Engineering, University of Connecticut, Storrs, CT, USA. (6) Department of Immunology, School of Medicine, Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut, 263 Farmington Ave, Farmington, CT, 06030-1601, USA. Srivastava@uchc.edu.
