Increased Sirtuin 6 Activity in Tumor Cells Can Prompt CD4-Positive T-Cell Differentiation Into Regulatory T Cells and Impede Immune Surveillance in the Microenvironment

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Sirtuin 6 (Sirt6) is expressed at increased levels in many tumors and may be involved in immunoregulation. The present study investigated how Sirt6 in tumor cells affects immune surveillance. Methods The human tumor cell lines A2780, HeLa, Huh7, MBA-MD-231, SMMC-7721 and SW480 were incubated with UBCS039, a target-selective activator of Sirt6, to stimulate Sirt6 activity. These cells, following washing to remove residual UBCS039, were cultured with human naive CD4 + T cells in the Transwell to observe the T cell differentiation. Regulatory T cells (Tregs) among CD4 + T cells and the levels of various cytokines and adenosine (ADO), an immunosuppressive metabolite, in the culture medium, were measured via flow cytometry. The treated tumor cells were examined via transcriptomic analysis. The transcriptomic results, as well as programmed cell death protein-1 (PD-1), programmed cell death-ligand 1 (PD-L1) and Sirt6 expression in tumor cells and CD4 + T cells were verified via real-time polymerase chain reaction (PCR). Results Following culture with UBSC039-pretreated tumor cells, the proportion of Tregs among CD4 + T cells was significantly increased. PD-L1 and Sirt6 expressions in UBS039-pretreated tumor cells and PD-1 expression in cocultured CD4 + T cells were also increased. Moreover, the ADO level increased, and the interleukin (IL)-10, interferon (IFN)-α2, IFN-γ and

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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