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• W2941036215 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, the ER stress sensor XBP1 was activated and regulated PD-1 and 2B4 transcription. Inhibiting XBP1 or reducing cholesterol in CD8+ T cells effectively restored antitumor activity. This study reveals a mechanism underlying T cell exhaustion and suggests a new strategy for restoring T cell function by reducing cholesterol to enhance T cell-based immunotherapy." @default.
• W2941036215 created "2019-05-03" @default.
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• W2941036215 date "2019-07-01" @default.
• W2941036215 modified "2023-10-16" @default.
• W2941036215 title "Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment" @default.
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• W2941036215 doi "https://doi.org/10.1016/j.cmet.2019.04.002" @default.
• W2941036215 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7061417" @default.
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