Cholesterol negatively regulates IL-9-producing CD8⁺ T cell differentiation and antitumor activity.

ABSTRACT: CD8⁺ T cells can be polarized into IL-9-secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8⁺ or CD4⁺ T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell per

SUBMITTER: Ma X 

PROVIDER: S-EPMC5987919 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature