Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells

Raykova, Ana; Carrega, Paolo; Lehmann, F.; Ivánek, Robert; Landtwing, Vanessa; Quast, Isaak; Lünemann, Jan D.; Finke, Daniela; Ferlazzo, Guido; Chijioke, Obinna; Münz, Christian

doi:10.1182/bloodadvances.2017008839

Cited by 40 publications

(34 citation statements)

References 46 publications

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“…Human ILC3s treated with IL-15 and IL-12 initiate the expression of NK cell cytotoxicity markers (Eomes, CD94, CD56 NKG2A, and NKG2C), suggesting a beneficial role for ILC3-NK plasticity in cancer (155,156). Plasticity between ILC3 and ILC1 mediated by IL-23 and also IL-12 produced by CD14 + DC promotes polarization from ILC3s toward ILC1s, which ultimately affects tumor immunosurveillance in response to various environmental changes (2,103,150).…”

Section: Ilc3s To Nk Cells Ilc1s and Ilc2smentioning

confidence: 99%

Pleiotropic Role and Bidirectional Immunomodulation of Innate Lymphoid Cells in Cancer

Flores-Borja

Irshad

et al. 2020

Front. Immunol.

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Innate lymphoid cells (ILCs) are largely tissue resident and respond rapidly toward the environmental signals from surrounding tissues and other immune cells. The pleiotropic function of ILCs in diverse contexts underpins its importance in the innate arm of immune system in human health and disease. ILCs derive from common lymphoid progenitors but lack adaptive antigen receptors and functionally act as the innate counterpart to T-cell subsets. The classification of different subtypes is based on their distinct transcription factor requirement for development as well as signature cytokines that they produce. The discovery and subsequent characterization of ILCs over the past decade have mainly focused on the regulation of inflammation, tissue remodeling, and homeostasis, whereas the understanding of the multiple roles and mechanisms of ILCs in cancer is still limited. Emerging evidence of the potent immunomodulatory properties of ILCs in early host defense signifies a major advance in the use of ILCs as promising targets in cancer immunotherapy. In this review, we will decipher the non-exclusive roles of ILCs associated with both protumor and antitumor activities. We will also dissect the heterogeneity, plasticity, genetic evidence, and dysregulation in different cancer contexts, providing a comprehensive understanding of the complexity and diversity. These will have implications for the therapeutic targeting in cancer.

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Section: Ilc3s To Nk Cells Ilc1s and Ilc2smentioning

confidence: 99%

Pleiotropic Role and Bidirectional Immunomodulation of Innate Lymphoid Cells in Cancer

Flores-Borja

Irshad

et al. 2020

Front. Immunol.

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“…In fact, the proinflammatory cytokine IL-12 was shown to induce the differentiation of ILC2s into IFNγ-producing ILC1s, a process that was reversed by IL-4 (89,90). Further, IL-12 mediates the conversion of ILC3s into type 1-like ILCs in a variety of pathological conditions (31,(91)(92)(93). The so-called "ex-ILC3s" were found to display cytotoxic activity in humans (93) and to effectively suppress tumor growth in a mouse model of melanoma (31).…”

Section: The Bidirectional Crosstalk Between Ilcs and Tumor Cells: Rementioning

confidence: 99%

“…Further, IL-12 mediates the conversion of ILC3s into type 1-like ILCs in a variety of pathological conditions (31,(91)(92)(93). The so-called "ex-ILC3s" were found to display cytotoxic activity in humans (93) and to effectively suppress tumor growth in a mouse model of melanoma (31). In the context of intestinal inflammation, the ILC3 to ILC1 plasticity was reversible in the presence of IL-23 (92).…”

Section: The Bidirectional Crosstalk Between Ilcs and Tumor Cells: Rementioning

confidence: 99%

The Interplay Between Innate Lymphoid Cells and the Tumor Microenvironment

2019

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The multifaceted roles of Innate Lymphoid Cells (ILC) have been widely interrogated in tumor immunity. Whereas, Natural Killer (NK) cells possess undisputable tumor-suppressive properties across multiple types of cancer, the other ILC family members can either promote or inhibit tumor growth depending on the environmental conditions. The differential effects of ILCs on tumor outcome have been attributed to the high degree of heterogeneity and plasticity within the ILC family members. However, it is now becoming clear that ILCs responses are shaped by their dynamic crosstalk with the different components of the tumor microenvironment (TME). In this review, we will give insights into the molecular and cellular players of the ILCs-TME interactions and we will discuss how we can use this knowledge to successfully harness the activity of ILCs for anticancer therapies.

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“…Additionally, recent reports hint towards the possibility of fully mature RORγt + ILC3 showing plasticity towards NK cells. One report described how human ILC3 from pediatric tonsils and from humanized mouse tissues have the ability to differentiate to cells displaying many characteristics of early-differentiated (stage 4) NK cells [ 83 ] (Fig. 1 ).…”

Section: Human Ilc Plasticitymentioning

confidence: 99%

The roles for innate lymphoid cells in the human immune system

et al. 2018

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From constituting a novel and obscure cell population, innate lymphoid cells (ILCs) are now accepted as a self-evident part of the immune system, contributing with unique and complementary functions to immunity by production of effector cytokines and interaction with other cell types. In this review, we discuss the redundant and complementary roles of the highly plastic human ILCs and their interaction with other immune cells with the ultimate aim of placing ILCs in a wider context within the human immune system.

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Interleukins 12 and 15 induce cytotoxicity and early NK-cell differentiation in type 3 innate lymphoid cells

Abstract: Key Points Human type 3 ILCs acquire features of early differentiated NK cells upon cytokine stimulation. IL-12 and IL-15–differentiated human ILC3s acquire cytotoxicity and kill leukemic targets.

Cited by 40 publications

References 46 publications

Pleiotropic Role and Bidirectional Immunomodulation of Innate Lymphoid Cells in Cancer

Pleiotropic Role and Bidirectional Immunomodulation of Innate Lymphoid Cells in Cancer

The Interplay Between Innate Lymphoid Cells and the Tumor Microenvironment

The roles for innate lymphoid cells in the human immune system

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