Striking a balance: the Goldilocks effect of CD8α expression on NK cells
Paarth B. Dodhiawala, Frank Cichocki
Paarth B. Dodhiawala, Frank Cichocki
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Commentary

Striking a balance: the Goldilocks effect of CD8α expression on NK cells

Abstract

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 CD8α, a coreceptor present on approximately 40% of human NK cells. IL-15 stimulation of CD8α– NK cells induced CD8α expression via the RUNX3 transcription factor, driving formation of a unique induced CD8α (iCD8α+) population. iCD8α+ NK cells displayed higher proliferation, metabolic activity, and antitumor cytotoxic function compared with preexisting CD8α+ and CD8α– subsets. Therefore, CD8α 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.

Authors

Paarth B. Dodhiawala, Frank Cichocki

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Figure 1

Activation by IL-15 generates induced CD8α+ NK cells.

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Activation by IL-15 generates induced CD8α+ NK cells. Cubitt et al. (11)...
Cubitt et al. (11) present three scenarios for human NK cells responding to IL-15. (A) In the first scenario, CD8α+ NK cells receive an IL-15 signal and become sustained CD8α+ NK cells. (B) In the second scenario, CD8α– NK cells with low expression of IL-15Rβ are activated by IL-15 and fail to upregulate CD8α, becoming persistent CD8α– NK cells. (C) In the third scenario, CD8α– NK cells with high expression of IL-15Rβ upregulate RUNX3 upon IL-15 stimulation and become induced CD8α+ NK cells. These cells exhibit several beneficial properties, including enhanced tumor control.