Analysis of chemokine gene expression/secretion showed that activation of pDCs and cDC2s led to biased expression of CXCR3/CCR5 (Th1)- and CXCR1/R2 (Th2/17)- associated ligands, respectively. CD8+αβ, CD56+, and γδ T and NK cells were recruited by activated pDC+/-cDC2-conditioned media in vitro, were detected by IHC in sections of, and by FACS in cultures of skin biopsies of melanoma patients vaccinated intradermally (ID) with activated pDCs and cDC2s, and were shown by spectral imaging clustered near DCs in the deep reticular dermis of melanoma patients injected ID with activated pDCs. cDC2s recruited CD4+ Th2/17, but not Th1, cells in vitro.
Contributed by Paula Hochman
ABSTRACT: Plasmacytoid dendritic cells (pDCs) and type 2 conventional dendritic cells (cDC2s) are currently under evaluation for use in cancer vaccines. Although both DC subsets can activate adaptive and innate lymphocytes, their capacity to recruit such cells is rarely considered. Here, we show that pDCs and cDC2s display a striking difference in chemokine secretion, which correlates with the recruitment of distinct types of immune effector cells. Activated pDCs express high levels of CXCR3 ligands and attract more CD8(+) T cells, CD56(+) T cells, and gammadelta T cells in vitro, compared to cDC2s. Skin from melanoma patients shows an influx of immune effector cells following intradermal vaccination with pDCs or cDC2s, with pDCs inducing the strongest influx of lymphocytes known to possess cytolytic activity. These findings suggest that combining both DC subsets could unite the preferred chemoattractive properties of pDCs with the superior T cell priming properties of cDC2s to ultimately enhance vaccine efficacy.