Int J Biol Sci 2020; 16(15):3075-3084. doi:10.7150/ijbs.49735

Research Paper

The NAD-dependent deacetylase SIRT2 regulates T cell differentiation involved in tumor immune response

Cui Jiang1,3, Jingwei Liu1, Min Guo1, Xiaoxin Gao4, Xuan Wu1, Ning Bai1, Wendong Guo1, Na Li1, Fei Yi1, Rong Cheng1, Hongde Xu1, Tingting Zhou1, Bo Jiang1, Tao Sun3, Shi Wei2✉, Liu Cao1✉

1. Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis, Treatment and Prevention, China Medical University, No. 77, Puhe Road, Shenyang North New Area, Shenyang, 110042, Liaoning, China.
2. Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35249-7331, USA.
3. Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and & Institute, 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning, China.
4. Central laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and & Institute, 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning, China.

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Citation:
Jiang C, Liu J, Guo M, Gao X, Wu X, Bai N, Guo W, Li N, Yi F, Cheng R, Xu H, Zhou T, Jiang B, Sun T, Wei S, Cao L. The NAD-dependent deacetylase SIRT2 regulates T cell differentiation involved in tumor immune response. Int J Biol Sci 2020; 16(15):3075-3084. doi:10.7150/ijbs.49735. Available from http://www.ijbs.com/v16p3075.htm

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Abstract

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 (TEM) cells in breast cancer patients. In keeping with these findings, altered T cells differentiation manifested as decreased TEM cells and increased naive T cells were observed in Sirt2 deficient mice. The upregulation of CD8+ TEM 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.

Keywords: SIRT2, T cell, differentiation, breast cancer