Targeting PIM1-Mediated Metabolism in Myeloid Suppressor Cells to Treat Cancer.

ABSTRACT: There is a strong correlation between myeloid-derived suppressor cells (MDSC) and resistance to immune checkpoint blockade (ICB), but the detailed mechanisms underlying this correlation are largely unknown. Using single-cell RNA sequencing analysis in a bilateral tumor model, we found that immunosuppressive myeloid cells with characteristics of fatty acid oxidative metabolism dominate the immune-cell landscape in ICB-resistant subjects. In addition, we uncovered a previously underappreciated role of a serine/threonine kinase, PIM1, in regulating lipid oxidative metabolism via PPARγ-mediated activities. Enforced PPARγ expression sufficiently rescued metabolic and functional defects of Pim1 ^-/- MDSCs. Consistent with this, pharmacologic inhibition of PIM kinase by AZD1208 t

SUBMITTER: Xin G 

PROVIDER: S-EPMC8137571 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature