Striking a balance: the Goldilocks effect of CD8[alpha] expression on NK cells

NK cells are cytotoxic innate immune cells involved in antitumor immunity, and they provide a treatment option for patients with acute myeloid leukemia (AML). In this issue of the JCI, Cubitt et al. investigated the role of CD8[alpha], a coreceptor present on approximately 40% of human NK cells. IL-15 stimulation of CD8[[alpha].sup.-] NK cells induced CD8[alpha] expression via the RUNX3 transcription factor, driving formation of a unique induced CD8[alpha] (iCD8[[alpha].sup.+]) population. iCD8[[alpha].sup.+] NK cells displayed higher proliferation, metabolic activity, and antitumor cytotoxic function compared with preexisting CD8[[alpha].sup.+] and CD8[[alpha].sup.-] subsets. Therefore, CD8[alpha] expression can be used to define a potential dynamic spectrum of NK cell expansion and function. Because these cells exhibit enhanced tumor control, they may be used to improve in NK cell therapies for patients with AML.