Metabolism in the tumor microenvironment: implications for pathogenesis and therapeutics

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• The immune system defends against pathogens, damage, and cancer.
• Immunotherapy, including immune checkpoint therapy (ICT) and adoptive cell transfer (ACT) with CAR T cells, aims to boost anti-cancer immunity.
• High resistance rates (60-80%) to ICT underscore the need to understand cancer immune suppression.

Purpose of the Study:

• To explore the potential of targeting the tumor microenvironment (TME) to overcome immunotherapy resistance.
• To investigate how TME metabolic reprogramming contributes to immune suppression in solid tumors.
• To discuss strategies for normalizing tumor vascularization and enhancing anti-tumor immunity by targeting TME metabolism.

Main Methods:

• Review of current understanding of the immunosuppressive TME in solid tumors.
• Analysis of metabolic stress factors within the TME, including nutrient competition and acidification.
• Discussion of potential therapeutic strategies targeting TME metabolism.

Main Results:

• Solid tumors (approx. 90% of cancers) create an immunosuppressive TME.
• TME dysfunction includes poor vascularization, impaired perfusion, and hypoxia.
• Metabolic stress in the TME activates immunosuppressive pathways.

Conclusions:

• Targeting TME metabolism offers a promising strategy to enhance immunotherapy efficacy.
• Modulating TME metabolism may normalize tumor vascularization and improve anti-tumor immune responses.
• Understanding TME metabolic reprogramming is crucial for developing more effective cancer therapies.