# The tumor microenvironment shapes gastric cancer progression by coordinating immune suppression and metabolic reprogramming

## TL;DR

This paper reviews how the tumor microenvironment in gastric cancer promotes cancer progression through immune suppression and metabolic changes.

## Contribution

The paper provides a comprehensive overview of the bidirectional interactions between gastric cancer cells and the tumor microenvironment.

## Key findings

- The tumor microenvironment supports immune evasion through regulatory T cells and macrophages.
- Metabolic reprogramming in gastric cancer includes glycolysis and altered lipid metabolism.
- ECM remodeling and signaling pathways like PI3K/AKT/mTOR and TGF-β drive cancer progression.

## Abstract

Gastric cancer (GC) remains a leading cause of cancer mortality, largely owing to metastasis driven by a highly dynamic tumor microenvironment (TME). Immunosuppressive regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) orchestrate immune evasion through checkpoint signaling and polarization programs, while cancer-associated fibroblasts (CAFs) reshape stromal architecture and promote hypoxia. Concurrently, ECM remodeling—mediated by integrins, growth factors, and matrix metalloproteinases—activates oncogenic pathways such as PI3K/AKT/mTOR, MAPK/ERK, and TGF-β to drive dissemination. Metabolic reprogramming, including glycolysis-derived lactate accumulation, fatty acid and cholesterol dysregulation, and altered amino acid utilization, further constrain antitumor immunity and support angiogenesis and therapeutic resistance. This review summarizes recent advances in the bidirectional crosstalk between GC cells and key TME components, emphasizing how immune remodeling, extracellular matrix (ECM) reprogramming, and metabolic rewiring converge to sustain tumor progression, while highlighting integrative signaling networks linking immune cells, ECM, and metabolites, and providing emerging opportunities for multi-target strategies that disrupt TME-dependent metastasis.