Cholesterol Induces CD8⁺ T Cell Exhaustion in the Tumor Microenvironment.

ABSTRACT: Tumor-infiltrating T cells often lose their effector function; however, the mechanisms are incompletely understood. We report that cholesterol in the tumor microenvironment induces CD8⁺ T cell expression of immune checkpoints and exhaustion. Tumor tissues enriched with cholesterol and cholesterol content in tumor-infiltrating CD8⁺ T cells were positively and progressively associated with upregulated T cell expression of PD-1, 2B4, TIM-3, and LAG-3. Adoptively transferred CD8⁺ T cells acquired cholesterol, expressed high levels of immune checkpoints, and became exhausted upon entering a tumor. Tumor culture supernatant or cholesterol induced immune checkpoint expression by increasing endoplasmic reticulum (ER) stress in CD8⁺ T cells. Consequently,

SUBMITTER: Ma X 

PROVIDER: S-EPMC7061417 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature