AccScience Publishing / MI / Online First / DOI: 10.36922/MI026050014
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COMMENTARY

SOAT1 as a metabolic immune checkpoint: Reprogramming lipid metabolism to inflame hepatocellular carcinoma

Yijia Shi1,2 ,  Yao Feng1,2 ,  Yibing Huang3 ,  Songlin Wang1,4,5* ,  Mo Chen1,2*
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1 Laboratory of Oral Homeostatic Medicine, School of Medicine and SUSTech Homeostatic Medicine Institute (SHMI), Southern University of Science and Technology, Shenzhen, Guangdong, China
2 Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine and SUSTech Homeostatic Medicine Institute (SHMI), Southern University of Science and Technology, Shenzhen, Guangdong, China
3 Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China
4 Laboratory of Oral Health and Homeostatic Medicine, School of Stomatology and Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China
5 Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medicine, Beijing, China
MI, 026050014 https://doi.org/10.36922/MI026050014
Received: 27 January 2026 | Revised: 16 February 2026 | Accepted: 17 March 2026 | Published online: 29 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Hepatocellular carcinoma is characterized by profound metabolic reprogramming and immune evasion, yet the mechanisms by which lipid metabolism intersects with antitumor immunity remain incompletely understood. Recent work by Ma et al. identifies sterol O-acyltransferase 1 (SOAT1) as a metabolic immune checkpoint in HCC. Beyond its canonical role in cholesterol esterification, SOAT1 inhibition disrupts lipid homeostasis, triggering lipotoxic stress, reactive oxygen species production, and endoplasmic reticulum stress that converge on NF-κB activation. This metabolic-inflammatory cascade drives chemokine secretion, recruits antigen-presenting cells and cytotoxic T cells, and converts immunologically “cold” tumors into inflamed ones. Importantly, pharmacological SOAT1 inhibition synergizes with PD-1 blockade, highlighting a tractable strategy to reprogram the tumor microenvironment and enhance immunotherapy efficacy in hepatocellular carcinoma.

Keywords
Sterol O-acyltransferase 1
Lipid metabolic reprogramming
Tumor immune microenvironment
NF-κB signaling
Hepatocellular carcinoma
Funding
S.W. is supported by the Beijing Municipal Government (Beijing Laboratory of Oral Health, grants PXM2021_014226_000041 and PXM2021_014226_000020; Beijing Scholar Program, grant PXM2018_014226_000021), the National Natural Science Foundation of China (grants 82030031 and 92149301), and the Chinese Research Unit of Tooth Development and Regeneration, Academy of Medical Sciences (grant 2019- 12M-5-031). M.C. is supported by the National Natural Science Foundation of China (grants 32541042 and 32400577), the Guangdong Province Basic and Applied Basic Research Foundation (grant 2023A1515110237), the Science and Technology Foundation of Shenzhen (grant JCYJ20240813094605008), and the Guangdong Province Higher Education Teaching Quality and Reform Project (grant SJZLGC202417). Y.F. is supported by the National Natural Science Foundation of China (grant 824B2025). Y.H. is supported by the Joint Funds for the Innovation of Science and Technology, Fujian Province (grant 2025Y9410) and the Startup Fund for Scientific Research, Fujian Medical University (grant 2024QH1166).
Conflict of interest
The authors declare no competing interests.
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Microbes & Immunity, Electronic ISSN: 3029-2883 Print ISSN: 3041-0886, Published by AccScience Publishing
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