Tumor-Derived Lactic Acid Modulates Dendritic Cell Activation and Differentiation.

Abstract The tumor milieu can influence DC differentiation in vivo and in vitro. We analyzed DC differentiation in a 3-dimensional tumor model and propose a new mechanism of DC modulation by the tumor environment. Monocytes were cultured in the presence of IL-4 and GM-CSF within multicellular tumor spheroids (MCTS) generated from urothelial carcinoma (J82, UMUC3) and melanoma cell lines (MelIm, Mel108). Monocytes invaded the tumor spheroids and differentiated into tumor-associated dendritic cells (TADC) that displayed an altered phenotype compared to DC generated without tumor contact. The expression of CD1a was reduced on TADC whereas CD80, CD86 and CD16 were upregulated. In addition, TADC…