MINI REVIEW article
Front. Immunol.
Sec. Systems Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1639823
This article is part of the Research TopicUnraveling Immune Metabolism: Single-Cell & Spatial Transcriptomics Illuminate Disease DynamicsView all 8 articles
The Impact of Aberrant Lipid Metabolism on the Immune Microenvironment of Gastric Cancer: A Mini Review
Provisionally accepted
- Zhejiang Chinese Medical University, Hangzhou, China
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Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with limited responses to immune checkpoint blockade (ICB) therapies in most patients. Increasing evidence indicates that the tumor immune microenvironment (TIME) plays a crucial role in immunotherapy outcomes. Among various metabolic abnormalities in the TIME, dysregulated lipid metabolism has emerged as a critical determinant of immune cell fate, differentiation, and function. In this review, we comprehensively summarize the current understanding of the immune landscape in GC, focusing on how altered lipid metabolism reshapes immune cell populations-including tumorassociated macrophages (TAMs), dendritic cells (DCs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and cytotoxic CD8⁺ T cells. We highlight key metabolic pathways such as fatty acid oxidation(FAO), cholesterol homeostasis, and lipid uptake that impact immune cell activity, contributing to immune evasion and therapeutic resistance. Importantly, we explore emerging therapeutic strategies targeting lipid metabolism, including inhibitors of cluster of differentiation 36 (CD36), fatty acid synthase (FASN), and sterol regulatory element-binding protein 1 (SREBP1) and discuss their synergistic potential when combined with ICB therapies. In conclusion, lipid metabolic reprogramming represents a promising yet underexplored axis in modulating antitumor immunity in GC. Integrating metabolic intervention with immunotherapy holds potential to overcome current treatment limitations and improve clinical outcomes. Future studies incorporating spatial omics and single-cell profiling will be essential to elucidate cell-type specific metabolic dependencies and foster translational breakthroughs.
Keywords: gastric cancer, Lipid Metabolism, Tumor immune microenvironment, CD8+ T cells, Tumor-associated macrophages, Immunotherapy resistance, fatty acid oxidation, Immune checkpoint blockade
Received: 02 Jun 2025; Accepted: 23 Jul 2025.
Copyright: © 2025 Chen, Chen, Xu, Li, Yu, He and Qiu. 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:
Shuangyu Chen, Zhejiang Chinese Medical University, Hangzhou, China
Yibo He, Zhejiang Chinese Medical University, Hangzhou, China
Shengliang Qiu, Zhejiang Chinese Medical University, Hangzhou, China
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