AMD1-driven MTA production sustains chemoresistance by rewiring PMN-MDSC immunosuppression

AMD1-driven 5'-methylthioadenosine (MTA) production in chemoresistant tumors sustains PMN-MDSC immunosuppression, linked to drug resistance via JAK-STAT3 signaling.

• Why it matters: Chemoresistant tumors can remodel the immune microenvironment, but how they maintain immunosuppressive PMN-MDSCs to preserve therapy resistance is unclear.
• What they did: Metabolomic profiling identified MTA released by resistant tumor cells; MTA enhanced PMN-MDSC suppression of CD8+ T cells by boosting JAK-STAT3, via binding PTPN2. AMD1 inhibition genetically or pharmacologically reduced MTA levels.
• The result: Lowering AMD1 reduced MTA, weakened PMN-MDSC immunosuppressive function, and re-sensitized resistant tumors to chemotherapy and immunotherapy.

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