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. 2018 Jun;2(6):341-346.
doi: 10.1038/s41551-018-0250-x. Epub 2018 Jun 11.

Towards superior dendritic-cell vaccines for cancer therapy

Mansi Saxena  1 , Sreekumar Balan  1 , Vladimir Roudko  1 , Nina Bhardwaj  2   3
Affiliations

Towards superior dendritic-cell vaccines for cancer therapy

Mansi Saxena et al. Nat Biomed Eng. 2018 Jun.
No abstract available

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Conflict of interest statement

Competing interests N.B. is on the senior advisory board of Check Point Sciences, Curevac, Neon and Inception, and a consultant for Genentech. All potential conflicts of interest are being managed by the Conflict of Interest Office, Icahn School of Medicine at Mount Sinai. M.S., S.B. and V.R. declare no competing interests.

Figures

Fig. 1 |
Fig. 1 |. Classical and newly discovered DC subsets.
DCs have been divided into several subsets, namely conventional DCs (cDC1, cDC2), plasmacytoid DCs (pDCs), Langerhan cells (LCs) and inflammatory DCs (iDCs), according to their functional properties and phenotype. Cell surface markers generally used to identify these subsets from blood and tissue are listed with each cell type. cDC1 and cDC2 can present antigens on MHC-I and MHC-II, and can thus activate both CD8+ and CD4+ T cells. cDC1 are primarily lymph-node-resident DCs recognized for their exceptional capacity for antigen crosspresentation and for activating CD8+ T cells. They can secrete high levels of type-I and type-III IFNs and IL-12 when stimulated with double-stranded RNA (dsRNA) poly-IC:LC (poly-inosinic and poly-cytidylic acids stabilized with poly-lysine). cDC2 are migratory DCs known for activating CD4+ T cells and for secreting high levels of IL-12 on activation. pDCs are primarily type-I IFN-secreting cells, and play a role in activating other DC subsets, T cells and B cells. Single-cell sequencing and unbiased genome classification of HLA-DR+Lin− cells isolated from blood suggests the existence of additional DC subsets (dotted lines), namely CD1c+_A, CD1c+_B and Axl+SIGLEC6+ DCs (AS-DCs). CD1c+_A and CD1c+_B are new subsets found within conventional cDC2 (CD1c+). The newly described AS-DC subset bears phenotypic markers similar to those found in both pDC and CD1c subsets, but deeper analysis revealed that AS-DCs were functionally distinct from pDCs despite their phenotypic similarity.
Fig. 2 |
Fig. 2 |. Expression of selected immune checkpoint factors on in vitro stimulated CD141+ DCs, MoDCs and pDCs.
Different DC subsets display a unique pattern of expression for inhibitory and activating checkpoints both at basal levels and on activation. CD141+ DCs and MoDCs were differentiated from CD34+ precursors and monocytes, respectively. Natural pDCs were sorted from blood of healthy donors. The original microarray datasets were analysed using the statistical package limma in R. Expression values are normalized by housekeeping gene expression, and were log2 transformed; mean values are shown on the heatmap. a, Inhibitory immune-checkpoint interactions. b, Stimulatory immune-checkpoint interactions. LPS, lipopolysaccharide-TLR4 agonist; Gardiquimod, TLR7 agonist; ODN2216, Class A CpG oligonucleotide-human TLR9 ligand.
See this image and copyright information in PMC

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