Gut Bacteria Induce Granzyme B Expression in Human Colonic ILC3s In Vitro in an IL-15–Dependent Manner

Castleman, Moriah J.; Dillon, Stephanie M.; Thompson, Tezha A.; Santiago, Mario L.; McCarter, Martin D.; Barker, Edward; Wilson, Cara C.

doi:10.4049/jimmunol.2000239

Cited by 7 publications

(2 citation statements)

References 71 publications

(69 reference statements)

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“…These data suggest that Granzyme B might have other functions, alternative to inducing target cell apoptosis. It was recently shown that ILC3s from the gut were able to express Granzyme B upon bacterial stimulation ( 48 ). Furthermore, Granzyme B has the ability to remodel the extracellular matrix by inducing anoikis and detachment of tumor cells, which prevents tumor cell migration and invasion ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Human ILC3 Exert TRAIL-Mediated Cytotoxicity Towards Cancer Cells

et al. 2022

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Group 3 helper Innate Lymphoid Cells (ILC3s) are cytokine-producing lymphocytes that respond to stress signals released during disturbed tissue homeostasis and infection. Upon activation, ILC3s secrete IL-22 and IL-17, and orchestrate immune responses against extracellular pathogens. Their role in cancer remains poorly explored. To determine their anti-cancer effector potential, we co-cultured cytokine-activated human ILC3s with cancer cells of different origins. ILC3s were able to directly respond to tumor cells, resulting in enhanced IFN-γ production. Upon tumor cell encounter, ILC3s maintained expression of the transcription factor RORγt, indicating that ILC3s preserved their identity. ILC3s were able to directly kill both hepatocellular carcinoma and melanoma tumor cells expressing cell-death receptor TRAILR2, through the activation of Caspase-8 in target cells. Moreover, liver-derived cytokine-activated ILC3s also expressed TRAIL and were able to eliminate hepatoblastoma cells. Together, our data reveal that ILC3s can participate in anti-tumor immune response through direct recognition of tumor cells resulting in IFN-γ release and TRAIL-dependent cytotoxicity. Thus, ILC3s might be ancillary players of anti-tumor immunity in tissues, acting as primary responders against transformed or metastasizing cells, which might be further exploited for therapies against cancer.

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Section: Discussionmentioning

confidence: 99%

Human ILC3 Exert TRAIL-Mediated Cytotoxicity Towards Cancer Cells

et al. 2022

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“…Ultimately, granzyme B expression of ILC3s is increased, with some ILC3 subsets even co-expressing perforin to exert a cytotoxic effect similar to NK cells ( Fig. 1 ) ( 42 ).…”

Section: Introductionmentioning

confidence: 99%

The interplay between innate lymphoid cells and microbiota

Wang,

Cui,

Yang

2023

mBio

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Innate lymphoid cells (ILCs) are mainly resident in mucosal tissues such as gastrointestinal tract and respiratory tract, so they are closely linked to the microbiota. ILCs can protect commensals to maintain homeostasis and increase resistance to pathogens. Moreover, ILCs also play an early role in defense against a variety of pathogenic microorganisms including pathogenic bacteria, viruses, fungi and parasites, before the intervention of adaptive immune system. Due to the lack of adaptive antigen receptors expressed on T cells and B cells, ILCs need to use other means to sense the signals of microbiota and play a role in corresponding regulation. In this review, we focus on and summarize three major mechanisms used in the interaction between ILCs and microbiota: the mediation of accessory cells represented by dendritic cells; the metabolic pathways of microbiota or diet; the participation of adaptive immune cells.

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