The hypoxic conditions of the TME induce functional impairments in NK cell effectors, such as downregulation of NKG2D, NKp30, and CD16, upregulation of immunosuppressive molecules like TIGIT, PD-L1, PD1, and TIM3, and promotion of autophagy-induced degradation of granzyme B.112,113 The hypoxia also leads to the accumulation of adenosine in the TME, which inhibits the anti-tumor function of NK cells through their adenosine A2A receptor.114. The gene discussed is GZMB; the disease is neoplasm.