Expression of Cationic XXXX Transporter 2 Is Required for Myeloid-Derived Suppressor Cell-Mediated Control of T Cell Immunity.

@entity32 @entity8561 @entity1069 @entity23233 @entity5 @entity19 @entity534 @entity13633 @entity3689
UNASSIGNED: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells that expand during benign and @entity5 -associated @entity32 and are characterized by their ability to inhibit T cell immunity. Increased metabolism of @entity8561 ( @entity534 ), through the enzymes arginase 1 and @entity13633 ( @entity13633 ), is well documented as a major MDSC suppressive mechanism. Therefore, we hypothesized that restricting MDSC uptake of @entity534 is a critical control point to modulate their suppressor activity. Using @entity19 models of prostate-specific @entity32 and @entity5 , we have identified the mechanisms by which extracellular @entity534 is transported into MDSCs. We have shown that MDSCs recruited to localized @entity32 and @entity5 sites upregulate cationic @entity3689 transporter 2 (Cat2), coordinately with @entity23233 and @entity13633 . Cat2 expression is not induced in MDSCs in peripheral organs. CAT2 contributes to the transport of @entity534 in MDSCs and is an important regulator of MDSC suppressive function. MDSCs that lack CAT2 have significantly reduced suppressive ability ex vivo and display impaired capacity for regulating T cell responses in vivo as evidenced by increased T cell expansion and decreased @entity5 growth in Cat2(-/-) @entity19 . The abrogation of suppressive function is due to low intracellular @entity534 levels, which leads to the impaired ability of @entity13633 to catalyze @entity534 -dependent metabolic processes. Together, these findings demonstrate that CAT2 modulates MDSC function. In the absence of CAT2, MDSCs display diminished capacity for controlling T cell immunity in @entity1069 and @entity5 models, where the loss of CAT2 results in enhanced antitumor activity.
