Abstract
Simple SummaryAcute myeloid leukemia (AML) is an aggressive form of cancer found in the blood and bone marrow with poor survival rates. Patients with AML are known to have many defects in their immune system which render immune cells unable to detect and/or kill cancer cells. Natural Killer (NK) cells are innate immune effector cells responsible for surveying the body to eliminate cancer cells as well as alert other immune cells to help clear the cancer cells. NK cells have developmental and functional defects in AML patients. While advances have been made to understand these NK cell defects in the setting of AML, the role of other closely related and recently discovered members of the innate lymphoid cell (ILC) family is much less clear. The ILC family is comprised of NK cells, ILC1s, ILC2s, and ILC3s, and due in part to their recent discovery, non-NK ILCs are just now beginning to be investigated in the setting of AML. By better understanding how AML alters the normal function of these cell types, and how the alteration regulates AML growth, we may be able to target and tailor new forms of therapy for patients.Over the past 50 years, few therapeutic advances have been made in treating acute myeloid leukemia (AML), an aggressive form of blood cancer, despite vast improvements in our ability to classify the disease. Emerging evidence suggests the immune system is important in controlling AML progression and in determining prognosis. Natural killer (NK) cells are important cytotoxic effector cells of the innate lymphoid cell (ILC) family that have been shown to have potent anti-leukemic functions. Recent studies are now revealing impairment or dysregulation of other ILCs in various types of cancers, including AML, which limits the effectiveness of NK cells in controlling cancer progression. NK cell development and function are inhibited in AML patients, which results in worse clinical outcomes; however, the specific roles of other ILC populations in AML are just now beginning to be unraveled. In this review, we summarize what is known about the role of ILC populations in AML.
Highlights
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While the expression patterns of CD200R1 are still being studied in the context of human innate lymphoid cell (ILC), it should be noted that this correlation may be the result of increased ILC1s in CD200Hi acute myeloid leukemia (AML), which would corroborate the observation of reduced cytotoxicity which is commonly associated with an ILC1-like phenotype
The results demonstrated that reconstitution of donor ILC1s (LinCD127+CRTH2-CD117-NKp44-), ILC2s (Lin-CD127+CRTH2+), and NKp44- ILC3s (LinCD127+CRTH2-CD117 NKp44, discussed in preceding paragraph) was slow compared to the rate of monocyte and neutrophil recovery, while NKp44 + ILC3s (Lin-CD127+CRTH2CD117+NKp44+) reconstituted more quickly relative to the other ILC subsets and at higher levels than found at steady-state
Summary
Since their discovery more than 50 years ago, NK cells have been extensively studied for their ability to detect and kill malignant or virally infected cells without prior exposure to specific stimuli. NK cell defects, namely loss of CD56bright cells with retention of the CD56dim subset [46] This NK cell defect is present even in patients without MDS or AML who still possess loss of function GATA2 mutations. Studies have demonstrated therapeutic interventions capable of inducing surface expression of other activating receptors that can further improve the capacity of NK cells to target and kill leukemic targets, including treatment with IL-15 [51] These studies suggest NK cell functional defects are at least partially reversible, indicating that further research may be able to optimize endogenous NK cell function in AML patients. NK cell function closely correlates with clinical outcomes in AML patients, but whether this correlation translates to “cause and effect” is still under investigation
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