Immune cell metabolic reprogramming mediates ICI therapy resistance

Area of Science:

• Immunology
• Oncology
• Metabolic pathways

Background:

• Immune checkpoint inhibitors (ICIs) have transformed advanced cancer treatment.
• Therapy resistance in solid tumors limits ICI efficacy.
• Metabolic reprogramming of immune cells within the tumor microenvironment (TME) is a key driver of this resistance.

Purpose of the Study:

• To review metabolic reprogramming in immune cells within the TME.
• To dissect molecular mechanisms of ICI resistance.
• To summarize combination strategies targeting metabolic pathways to reverse ICI resistance.

Main Methods:

• Systematic review of literature on immune cell metabolism in the TME.
• Analysis of molecular mechanisms underlying metabolic adaptation in immune and cancer cells.
• Compilation of current combination strategies involving metabolic interventions.

Main Results:

• Immune cells in the TME undergo metabolic reprogramming, creating a 'metabolic cage'.
• Metabolic exhaustion of effector immune cells and metabolic adaptation of immunosuppressive cells contribute to tumor immune evasion.
• Metabolic reprogramming directly mediates resistance to ICIs.

Conclusions:

• Understanding TME metabolic reprogramming is crucial for overcoming ICI resistance.
• Targeting metabolic pathways in immune cells offers a promising strategy to enhance cancer immunotherapy efficacy.
• Combination therapies modulating metabolism hold translational potential for optimizing cancer treatment.