ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1575472
This article is part of the Research TopicCommunity Series in The Immunosuppressive Tumor Microenvironment and Strategies to Revert its Immune Regulatory Milieu for Cancer Immunotherapy: Volume IIView all 7 articles
Hypercholesterolemia and the role of lipid metabolism gene (CES1) in immune infiltration promote central nervous system relapse in acute myeloid leukemia
Provisionally accepted
- 1The Key Laboratory of Hematology of Jiangxi Province, Department of Hematology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
- 2The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nan Chang, Jiang Xi, China, NAN CHANG, China
- 3The University of Melbourne, Parkville, Victoria, Australia
- 4Clinical Trial Research Center, The Second Affiliated Hospital of Nanchang Universi, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, China
- 5Department of Geratology, The Second Affiliated Hospital of Nanchang University, NAN CHANG, China
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Background: Alterations in multiple lipid metabolism pathways are associated with cancer progression. However, it remains unknown regarding the association between lipid metabolism and central nervous system (CNS) relapse in acute myeloid leukemia (AML). Methods: We conducted a retrospective analysis of 806 AML cases to evaluate the link between serum lipid levels and CNS relapse risk. RNA-sequencing data from 895 AML patients were also obtained from the TARGET database to identify hub lipid metabolism-related genes (LMRGs) associated with CNS relapse, vivo and vitro experiments to validate the results of bioinformatics analysis . Results: Patients with CNS relapse exhibited significantly elevated levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) compared to the non-CNS relapse group. Hypercholesterolemia is a risk factor of CNS relapse . RNA sequencing of AML patients with or without CNS relapse disclosed 1,368 differentially expressed genes (DEGs). Functional enrichment analysis of DEGs showed a connection between lipid metabolism and CNS relapse. Through a integrating these DEGs, LMRGs, and whole-genome correlation network analysis (WGCNA), CES1 was identified as a hub LMRG. High CES1 expression is a risk factor of CNS relapse and shorter overall survival. Moreover, CES1 affected the proportion of 9 types of tumor-infiltrating immune cells (TICs), especially Macrophage M2, which supported by functional results of CES1's knockdown and overexpression in AML cells and AML xenograft tumor model. Conclusion: Hypercholesterolemia and CES1 can promote CNS relapse in AML patients, especially depending on CES1's potential to modify immune infiltration in the TME.
Keywords: Central Nervous System, Leukemia, Hyperlipidemia, CES1, Tumor Microenvironment, Estimate, CIBERSORT, Acute Myeloid Leukemia
Received: 12 Feb 2025; Accepted: 01 Jul 2025.
Copyright: © 2025 Bao, Tu, Zhang, Jiang, Chen, Tu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jian Li, Clinical Trial Research Center, The Second Affiliated Hospital of Nanchang Universi, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, China
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