Activation of human pluripotent stem cell-derived dendritic cells by cancer cell co-culture

Human pluripotent stem cells (hPSCs) are considered a source of cell therapy. Dendritic cells (DCs) derived from hPSCs (hPSC-DCs) are viewed as similar to fetal DCs. The latter, while mediating immune suppression, maintain fetal homeostasis. This study looks at the outcomes of a protocol designed for massive and long-term generation of hPSCDCs in a serum-free cell culture. When cultured in serum-free media, the newly generated pure populations of immature hPSC-DCs featured significant stability. Such DCs exhibited the typical morphology, active phagocytosis, and were highly motile. The cells expressed on the outer cell membrane specific well-known DC markers, CD11c, CD86, and CD45, while were negative for CD14, the key macrophage marker. Attempts to activate the hPSC-DCs through proinflammatory factors failed to induce IL-12 secretion and cell surface expression of HLA-DR. Yet, they elicited the expression of several genes encoding markers that belong to the conventional DC subset 1 (cDC1). Co-culturing hPSC-DCs with thyroid cancer cells entailed secretion of IL-12 and, in a fraction of the population, strong cell surface expression of HLA-DR and other markers of activated DCs. Our observations suggest that hPSC-DCs require necrotic cancer cell-derived damage-associated molecular patterns (DAMPs) for their activation.