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With regard to glutamine metabolism, inhibition of glutamine utilization has likewise been incorporated into the clinical development strategy of metabolic targeting plus immunotherapy. Animal studies have shown that JHU083, a prodrug of the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON), not only suppresses tumor growth, but also reshapes the transcriptional profile and antigen-presentation/inflammatory cytokine characteristics of tumor-associated macrophages, shifting them from an immunosuppressive tendency toward a functional state more favorable for antitumor immunity (118)

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