Metabolic Regulation of Immune Responses: Molecular Mechanisms, Diseases, and Therapeutic Targets

Area of Science:

• Oncology
• Immunology
• Metabolism

Background:

• Cancer metabolic reprogramming significantly alters the tumor microenvironment (TME), driving immune evasion and therapeutic resistance.
• Metabolic enzymes are increasingly recognized as key regulators of immune signaling, cell fate, and immune checkpoint expression within the TME.

Purpose of the Study:

• To elucidate complex immunometabolic networks by examining fructose-1,6-bisphosphatase 1 (FBP1) as a model metabolic gatekeeper.
• To synthesize recent advances on how metabolic rewiring drives tumor progression, immune suppression, and immunotherapy resistance.

Main Methods:

• Review of canonical metabolic effects and noncanonical signaling mechanisms of key metabolic enzymes like FBP1.
• Analysis of immune evasion mechanisms including STAT3-PD-L1 regulation, innate immune surveillance, T cell exhaustion, and stromal remodeling.
• Exploration of emerging therapeutic strategies targeting immunometabolic pathways.

Main Results:

• Metabolic dysregulation, exemplified by FBP1, promotes tumor progression through altered bioenergetics and signaling.
• Metabolic rewiring contributes to immune suppression by affecting immune cell function and checkpoint expression.
• Specific mechanisms of immune evasion and TME remodeling are driven by metabolic alterations.

Conclusions:

• Targeting immunometabolic pathways presents promising therapeutic strategies, including small molecules, vitamin/gene therapies, and nanotechnology.
• Challenges such as metabolic heterogeneity and context-dependent enzyme function require further investigation.
• Biomarker-guided precision strategies are crucial for translating immunometabolic insights into safe and effective cancer therapies.