Lactate Induces Pro-tumor Reprogramming in Intratumoral Plasmacytoid Dendritic Cells.

ABSTRACT: Plasmacytoid dendritic cells are the most efficient producers of type I interferons, viz. IFNα, in the body and thus have the ability to influence anti-tumor immune responses. But repression of effective intra-tumoral pDC activation is a key immuno-evasion strategy exhibited in tumors-tumor-recruited pDCs are rendered "tolerogenic," characterized by deficiency in IFNα induction and ability to expand regulatory T cells in situ. But the tumor-derived factors that drive this functional reprogramming of intra-tumoral pDCs are not established. In this study we aimed at exploring if intra-tumoral abundance of the oncometabolite lactate influences intra-tumoral pDC function. We found that lactate attenuates IFNα induction by pDCs mediated by intracellular Ca²⁺ mobilization trigg

SUBMITTER: Raychaudhuri D 

PROVIDER: S-EPMC6692712 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature