A new cancer immunotherapy based on cholesterol metabolism modulation

BAI Yibing; XU Chenqi

doi:10.3981/j.issn.1000-7857.2018.07.005

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Science & Technology Review ›› 2018, Vol. 36 ›› Issue (7) : 33-36. DOI: 10.3981/j.issn.1000-7857.2018.07.005

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A new cancer immunotherapy based on cholesterol metabolism modulation

Author information -

1. Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China;
2. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

Abstract

Immune checkpoint blockade and other cancer immunotherapies have achieved great success in clinic but problems such as low response rate still remain. Cholesterol is a key component of cell membrane, whose cellular metabolism can influence the plasma membrane environment and effector function of T cells. We have found that the anti-tumor immune response of CD8⁺ T cells can be potentiated by modulating cellular cholesterol metabolism. Inhibiting the activity of ACAT1, a key cholesterol esterification enzyme, can upregulate the cholesterol level on CD8⁺ T cell plasma membrane, and significantly enhance the anti-tumor effector function. This finding provides a new method for cancer immunotherapy.

Key words

CD8⁺ T cells / cholesterol metabolism / ACAT1 / anti-tumor immunity

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BAI Yibing, XU Chenqi. A new cancer immunotherapy based on cholesterol metabolism modulation[J]. Science & Technology Review, 2018, 36(7): 33-36 https://doi.org/10.3981/j.issn.1000-7857.2018.07.005

References

[1] US Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication[EB/OL]. (2017-05-30)[2018-01-10]. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm560040.htm.
[2] Vanpouillebox C, Lhuillier C, Bezu L, et al. Trial watch:Immune checkpoint blockers for cancer therapy[J]. Oncoimmunology, 2017, 6(11):e1373237.
[3] Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance:Immunoselection and immunosubversion[J]. Nature Reviews Immunology, 2006, 6(10):715-727.
[4] Mouritsen O G, Zuckermann M J. What's so special about cholesterol[J]. Lipids, 2004, 39(11):1101-1113.
[5] Roduit C, Goot F G V D, Rios P D L, et al. Elastic membrane heterogeneity of living cells revealed by stiff nanoscale membrane domains[J]. Biophysical Journal, 2008, 94(4):1521-1532.
[6] Fooksman D R, Vardhana S, Vasilivershamis G, et al. Functional anatomy of T cell activation and synapse formation[J]. Annual Review of Immunology, 2010, 28(1):79-105.
[7] Jenkins M R, Griffiths G M. The synapse and cytolytic machinery of cytotoxic T cells[J]. Current Opinion in Immunology, 2010, 22(3):308-313.
[8] Kaizuka Y, Douglass A D, Varma R, et al. Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells[J]. PNAS, 2007, 104(51):20296-202301.
[9] Brown M S, Goldstein J L. A receptor-mediated pathway for cholesterol homeostasis[J]. Science, 1986, 25(7):583-602.
[10] Goldstein J L, Deboseboyd R A, Brown M S. Protein sensors for membrane sterols[J]. Cell, 2006, 124(1):35-46.
[11] Tabas I. Consequences of cellular cholesterol accumulation:Basic concepts and physiological implications[J]. Journal of Clinical Investigation, 2002, 110(7):905-911.
[12] Yang W, Bai Y, Xiong Y, et al. Potentiating the antitumour response of CD8⁺ T cells by modulating cholesterol metabolism[J]. Nature, 2016, 531(7596):651-655.
[13] Chang T Y, Chang C C Y, Ohgami N, et al. Cholesterol sensing, trafficking, and esterification[J]. Annual Review of Cell & Developmental Biology, 2006, 22(1):129-157.
[14] Libby P, Aikawa M. Stabilization of atherosclerotic plaques:New mechanisms and clinical targets[J]. Nature Medicine, 2002, 8(11):1257-1262.
[15] Pal P, Gandhi H, Giridhar R, et al. ACAT inhibitors:The search for novel cholesterol lowering agents[J]. Mini Reviews in Medicinal Chemistry, 2013, 13(8):1195-1219.