Sirtuin 2 (SIRT2), an NAD+-dependent deacetylase, regulates multiple biologic and pathologic processes including mitosis, genomic integrity, cell homeostasis and tumorigenesis. However, the role of SIRT2 in the immune response to cancer remains largely elusive. In this study, we found significantly lower expression of SIRT2 in peripheral T lymphocytes from breast cancer patients when compared to normal individuals. Moreover, SIRT2 levels positively correlated with CD8⁺ effector memory T (T_EM) cells in breast cancer patients. In keeping with these findings, altered T cells differentiation manifested as decreased T_EM cells and increased naive T cells were observed in Sirt2 deficient mice. The upregulation of CD8⁺ T_EM by SIRT2 might attribute to the activation of aerobic oxidation as well as the inhibition of GSK3β acetylation in CD8⁺ T cells. Taken together, these results suggest that SIRT2 participate in tumor immune response by regulating T cell differentiation, which may provide novel insight for tumor prevention and immune therapy.

中文翻译：

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NAD依赖性脱乙酰酶SIRT2调节参与肿瘤免疫反应的T细胞分化

Sirtuin 2 (SIRT2) 是一种 NAD+ 依赖性脱乙酰酶，可调节多种生物学和病理过程，包括有丝分裂、基因组完整性、细胞稳态和肿瘤发生。然而，SIRT2 在对癌症的免疫反应中的作用在很大程度上仍然难以捉摸。在这项研究中，我们发现与正常个体相比，乳腺癌患者外周 T 淋巴细胞中 SIRT2 的表达显着降低。此外，SIRT2 水平与乳腺癌患者的 CD8 ⁺效应记忆 T (T _{EM ) 细胞呈正相关。}与这些发现一致，在Sirt2缺陷小鼠中观察到T 细胞分化的改变表现为 T _{EM细胞减少和幼稚 T 细胞增加。}CD8 ^+上调SIRT2 的T _EM可能归因于有氧氧化的激活以及 CD8 ⁺ T 细胞中 GSK3β 乙酰化的抑制。总之，这些结果表明 SIRT2 通过调节 T 细胞分化参与肿瘤免疫反应，这可能为肿瘤预防和免疫治疗提供新的见解。