018 Imiquimod perturbs amino acid metabolism in human CD8+ T cells

Imiquimod (IMQ), a TLR7 agonist, is standard local treatment for non-melanoma skin cancers (NMSC). IMQ triggers inflammation, ultimately resulting in immunological tumor destruction. Albeit promotes the recruitment of effector T (TE) cells, anergy CD4+ cells. Meanwhile, how affects human CD8+ TE pivotal to cancer control, remains unclear. To address this, we studied cell lines from NMSC and circulating, skin-homing CLA+CD8+ In both models, IMQ-treated cells showed significantly reduced proliferation IFN-γ production. Because metabolism fundamentally underlies function hypothesized that metabolic changes underlie suppressive effects on Along this idea, found have mTOR activity. gain broader insight into adaptations performed proteomics, revealing dysregulation amino acid (AA) transporters, especially SLC1A5 transporter intracellular levels AA transported by SLC1A5, including glutamine, asparagine, aspartic acid. Consistent with known supportive role several AA, glutamine responses, adding these restored functions. Our finding SLC1A5-dependent rescue IMQ-induced hypo-responsiveness provides rational studying if exogenous can improve effectiveness IMQ-based destructive therapies.