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INO binds A2A receptors with lower affinity than ADO and preferentially activates ERK1/2 over cAMP signaling ( Targeting the CD38/NAD + axis remains an attractive immunotherapeutic strategy in MM, but the broad expression of CD38 raises concerns about off-target toxicity ( Supplementary Table 1 ), ADA-based degradation ( + surrogates ( Overall, our findings indicate that anti-CD38 therapies engage a dynamic, compartmentalized adenosinergic network in MM, with metabolic adaptations that may influence therapeutic responses