Authors: Xiaozhen Zhang, Mengyi Lao, Kang Sun, Hanshen Yang, Lihong He, Xinyuan Liu, Linyue Liu, Sirui Zhang, Chengxiang Guo, Sicheng Wang, Jiatao Shi, Xiaoyu Zhang, Daqian Xu, Xiongbin Lu, Xueli Bai, Tingbo Liang
Published: 2025-05-21
Source: Full article
Dysregulated metabolism of immune cells in the tumor microenvironment leads to immune evasion and tumor progression. As a major cell component in the tumor, the metabolic reprogramming of tumor-associated macrophages (TAMs) creates an immunosuppressive microenvironment in hepatocellular carcinoma (HCC). Our study found that sphingolipid (particularly, sphingosine-1-phosphate or S1P) levels are a clinical indicator for prognosis and immunotherapy response in patients with HCC. S1P primarily derived from TAMs, where NIMA-related kinase 2 (NEK2) plays a key role in controlling the activity of serine palmitoyl-CoA transferase, a rate-limiting enzyme in S1P biosynthesis. The S1P produced by NEK2