Inosine is an alternative carbon source for CD8⁺-T-cell function under glucose restriction

Area of Science:

• Immunology
• Metabolic pathways
• Cancer biology

Background:

• T cells require significant metabolic reprogramming to meet demands after antigen stimulation.
• Effector T cells must adapt to nutrient availability at inflammation sites.

Purpose of the Study:

• To investigate if effector T cells can utilize inosine as an alternative metabolic substrate.
• To explore the therapeutic potential of inosine in anti-tumour immunity.

Main Methods:

• In vitro metabolic assays using effector T cells.
• Analysis of inosine metabolism via purine nucleoside phosphorylase.
• Assessment of inosine supplementation effects on anti-tumour therapies in vivo.

Main Results:

• Effector T cells metabolize inosine into substrates that support ATP production and biosynthesis.
• The ribose moiety of inosine enters central metabolic pathways.
• Inosine supplementation enhances anti-tumour efficacy of immune checkpoint blockade and adoptive T-cell transfer in specific solid tumours.

Conclusions:

• Inosine serves as a viable alternative nutrient for effector T cells, crucial for their function.
• Inosine can overcome tumour-imposed metabolic restrictions, improving T cell-mediated anti-tumour responses.
• Targeting inosine metabolism presents a potential strategy to enhance cancer immunotherapy.