MTOR and cancer: Ionic signals play a critical role in modulating adaptive antitumor immune responses.230 Tumors often contain regions of cellular necrosis, which are associated with poor patient prognosis across various cancer types.231 These necrotic areas release intracellular potassium ions into the TME, leading to an increase in the extracellular potassium concentration, which impairs TCR-driven Akt–mTOR signaling and the activation of effector programs to limit T cell functionality232 (Fig. 3c).