Lipid metabolism and the immune microenvironment in gastric cancer.

Authors

Zhuoyang Wang, Yichen Du, Qinglin Gu, Xinjie Liu, Ming Lu

Published in

Frontiers in immunology. Volume 17. Pages 1890119. Epub Aug 20, 2026.

Abstract

The treatment of gastric cancer (GC) has entered an era of precision medicine combining molecular subtyping, immune checkpoint inhibitors (ICIs), anti-human epidermal growth factor receptor 2 (HER2), anti-claudin 18.2 (CLDN18.2), anti-angiogenic therapy, and chemotherapy. However, efficacy remains limited by tumor microenvironment (TME) heterogeneity, immune exclusion, myeloid suppression, nutrient competition, and metabolic adaptation. Lipid metabolic reprogramming represents a class of mechanisms with high translational value among metabolic immune checkpoints in GC: it supports tumor-cell membrane synthesis, redox homeostasis, peritoneal/omental metastasis, and adaptation to therapeutic stress, while also affecting regulatory T cells (Tregs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells, and CD8+ T cells. This review focuses on cluster of differentiation 36 (CD36)-mediated fatty acid uptake; carnitine palmitoyltransferase 1A (CPT1A)-dependent fatty acid oxidation (FAO); fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), sterol regulatory element-binding protein 1 (SREBP-1), and stearoyl-CoA desaturase 1 (SCD1)-mediated de novo lipogenesis; cholesterol and lipid-droplet metabolism; lipid-mediated post-translational modifications; lipid peroxidation; and ferroptosis. Lipid metabolism-targeted therapy should be positioned as a biomarker-driven combination strategy rather than as non-selective monotherapy. Future studies should integrate single-cell and spatial transcriptomics with lipidomics, imaging mass spectrometry, and paired pre- and post-treatment biopsies to define cell type-specific lipid dependencies and pharmacodynamic markers. Clinical translation will require prospective validation that a candidate intervention changes the intended lipid pathway in the intended tumor or immune-cell compartment without disabling metabolically essential normal tissues.

PMID:
42694682
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.