Targeting SLC38A5 Overcomes αPD-1 Immunotherapy Resistance by Alleviating Glutamine Competition Between Glioblastoma Cells and T Cells.

Inhibiting SLC38A5 enhances αPD-1 immunotherapy response in glioblastoma by modulating tumor glutamine metabolism, leading to improved tumor control.

• Why it matters: Glioblastoma shows limited response to PD-1 checkpoint blockade, highlighting a critical need to understand resistance mechanisms and develop effective combination therapies.
• What they did: A CRISPR-Cas9 screen identified SLC38A5 as a key gene; its ablation in glioblastoma increased sensitivity to αPD-1 therapy by altering glutamine uptake and tumor microenvironment.
• The result: Targeting SLC38A5 with a nanobody improved immune response and suppressed tumor growth, offering a promising strategy to overcome immunotherapy resistance in glioblastoma.