Mechanisms of Metabolic Reprogramming Regulating Immunosuppression in the Gastric Cancer Tumor Microenvironment

Area of Science:

• Oncology
• Immunology
• Gastroenterology

Background:

• Immune checkpoint inhibitors (ICIs) are effective in melanoma and lung cancer but show limited benefit in gastric cancer (GC).
• Gastric cancer's heterogeneity and tumor microenvironment (TME) contribute to ICI resistance.
• Helicobacter pylori (H. pylori) infection is a significant factor in GC development and progression.

Purpose of the Study:

• To review the correlation between H. pylori infection, gastric physiology, and GC molecular subtypes.
• To emphasize the unique metabolic features of GC and their impact on immune response.
• To explore metabolic reprogramming in the GC TME and its role in immune suppression.

Main Methods:

• Literature review focusing on H. pylori infection, gastric physiology, GC metabolism, and immune TME.
• Analysis of molecular subtype-specific induction pathways in GC.
• Synthesis of current research on metabolic vulnerabilities and therapeutic strategies.

Main Results:

• H. pylori infection influences GC development and metabolic reprogramming.
• Specific metabolic features of GC contribute to an immunosuppressive TME.
• Immune metabolic reprogramming is linked to poor ICI response in GC.

Conclusions:

• Targeting metabolic vulnerabilities presents a promising therapeutic strategy for GC.
• Subtype-guided metabolic therapies may overcome the immunosuppressive TME in GC.
• Understanding GC's unique metabolism is crucial for improving immunotherapy outcomes.