Group‐2 Innate Lymphoid Cells Promote HCC Progression Through CXCL2‐Neutrophil‐Induced Immunosuppression

Xu, Xingyuan; Ye, Long‐Yun; Zhang, Qi; Shen, Hang; Li, Shanshan; Zhang, Xiaoyu; Ye, Mao

doi:10.1002/hep.31855

Cited by 58 publications

(59 citation statements)

References 41 publications

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“…This was confirmed in a recent study by Xu et al. where the abundance of ILC2s in the tumor area of HCC patients liver is correlated with poor prognosis ( 62 ). When looking closely at the phenotype, they identified a subset of ILC2s, enriched in the tumor tissue but absent in the non-tumoral area, lacking the expression of killer cell lectin-like receptor subfamily G member 1 (KLRG1), a known marker for mature and activated ILC2s.…”

Section: Pro- and Anti-tumoral Roles Of Ilcs In Hccsupporting

confidence: 62%

“…Co-cultures of murine hepatic ILC2s with Hepa1-6 cells resulted in significant decrease in KLRG1 levels. Hepa1-6 cells do not express E-cadherin but overexpression of its Cdh1 gene maintained KLRG1 expression in ILC2s ( 62 ). These experiments suggest that the loss of KLRG1 on ILC2s in HCC can be accounted for by a decrease in E-cadherin expression at the surface of hepatocytes.…”

Section: Pro- and Anti-tumoral Roles Of Ilcs In Hccmentioning

confidence: 99%

“…Klrg1 overexpression in ILC2s led to a decrease in Cxcl2 and Il-13 mRNA levels whereas Klrg1 knockout enhanced their expression. Neutrophils recruitment was also increased with the use of conditioned medium of Klrg1 -deficient ILC2s in a chemotaxis assay ( 62 ). An immunosuppressive profile was induced in recruited neutrophils via the upregulation of Arg1 , coding for Arginase 1.…”

Section: Pro- and Anti-tumoral Roles Of Ilcs In Hccmentioning

confidence: 99%

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Signaling Pathways Tuning Innate Lymphoid Cell Response to Hepatocellular Carcinoma

Bourayou

Golub

2022

Front. Immunol.

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Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide and its incidence continues to rise globally. Various causes can lead to its development such as chronic viral infections causing hepatitis, cirrhosis or nonalcoholic steatohepatitis (NASH). The contribution of immune cells to HCC development and progression has been extensively studied when it comes to adaptive lymphocytes or myeloid populations. However, the role of the innate lymphoid cells (ILCs) is still not well defined. ILCs are a family of lymphocytes comprising five subsets including circulating Natural Killer (NK) cells, ILC1s, ILC2s, ILC3s and lymphocytes tissue-inducer cells (LTi). Mostly located at epithelial surfaces, tissue-resident ILCs and NK cells can rapidly react to environmental changes to mount appropriate immune responses. Here, we provide an overview of their roles and actions in HCC with an emphasis on the importance of diverse signaling pathways (Notch, TGF-β, Wnt/β-catenin…) in the tuning of their response to HCC.

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Section: Pro- and Anti-tumoral Roles Of Ilcs In Hccsupporting

confidence: 62%

Section: Pro- and Anti-tumoral Roles Of Ilcs In Hccmentioning

confidence: 99%

Section: Pro- and Anti-tumoral Roles Of Ilcs In Hccmentioning

confidence: 99%

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Signaling Pathways Tuning Innate Lymphoid Cell Response to Hepatocellular Carcinoma

Bourayou

Golub

2022

Front. Immunol.

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“…Previous studies have shown a role for ILC2s in both tumour promotion and tumour rejection, which have been comprehensively summarized elsewhere 57 . However, over the past 2 years, considerable progress has been made in the understanding of how specific populations of ILC2s contribute to immunosurveillance in different types of cancer 58 – 62 (Fig. 2 ).…”

Section: Ilc2s In Cancermentioning

confidence: 99%

Heterogeneity of type 2 innate lymphoid cells

Spits

Mjösberg

2022

Nat Rev Immunol

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More than a decade ago, type 2 innate lymphoid cells (ILC2s) were discovered to be members of a family of innate immune cells consisting of five subsets that form a first line of defence against infections before the recruitment of adaptive immune cells. Initially, ILC2s were implicated in the early immune response to parasitic infections, but it is now clear that ILC2s are highly diverse and have crucial roles in the regulation of tissue homeostasis and repair. ILC2s can also regulate the functions of other type 2 immune cells, including T helper 2 cells, type 2 macrophages and eosinophils. Dysregulation of ILC2s contributes to type 2-mediated pathology in a wide variety of diseases, potentially making ILC2s attractive targets for therapeutic interventions. In this Review, we focus on the spectrum of ILC2 phenotypes that have been described across different tissues and disease states with an emphasis on human ILC2s. We discuss recent insights in ILC2 biology and suggest how this knowledge might be used for novel disease treatments and improved human health.

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“…Similarly, in another study, ILC2 infiltration was associated with better outcomes in patients with pancreatic ductal adenocarcinoma, and the antitumor function of ILC2s was found to be dependent on ILC2activating IL-33 (14). Conversely, another study showed that a higher infiltration of less-mature KLRG1 − ILC2 in HCC promoted tumor development, attributed to the possibility that ILC2s mediate immunosuppression in the tumor microenvironment through the KLRG1 − ILC2/ CXCL2/neutrophil pathway (15). The diverse functions of ILC2s on tumor regulation may be caused by multiple tumor types or by the influence of complicated cytokine networks.…”

Section: Editorialmentioning

confidence: 88%

Comment on: the tumour microenvironment shapes innate lymphoid cells in patients with hepatocellular carcinoma

Xu¹,

Yang²,

Tang³

2022

Hepatobiliary Surg Nutr

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide (1). Resident immune cell populations within the liver, which is considered the largest immune organ, increase the pathological complexity of HCC (2). Innate lymphoid cells (ILCs), recently identified leukocytes, are a family of innate immune cells with similar characters to T lymphocytes. ILCs largely exist in intestinal mucosal tissue and regulate intestinal inflammation, mucosal defense, and tissue repair in gut disease processes (3). Unlike T cells, ILCs lack antigenspecific receptors; therefore, they cannot directly mediate antigen-specific responses (4). However, they can be activated by cytokines and/or natural cytotoxic receptors (such as NKp44) (5). ILCs are a highly heterogeneous cell population with high plasticity. Based on the expression of transcription factors and the production of different cytokines, ILCs can be divided into ILC1, ILC2, and ILC3, which are counterparts of the three main helper T cell subsets (Th1, Th2, and Th17) (6). Although ILCs can be detected in various tumor types, their specific contribution to tumor immunity is yet to be thoroughly elucidated.In a recently published article in Gut, Heinrich et al. (7) discovered that ILC-controlling cytokines were differentially expressed in non-tumor and tumor tissues of patients with HCC. Among the differentially expressed cytokine genes, 3 cytokines (IL-1β, IL-33, and TGF-β) were shown to affect the plasticity and function of ILCs. Specifically, it was shown that TGF-β can affect the

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Group‐2 Innate Lymphoid Cells Promote HCC Progression Through CXCL2‐Neutrophil‐Induced Immunosuppression

Cited by 58 publications

References 41 publications

Signaling Pathways Tuning Innate Lymphoid Cell Response to Hepatocellular Carcinoma

Signaling Pathways Tuning Innate Lymphoid Cell Response to Hepatocellular Carcinoma

Heterogeneity of type 2 innate lymphoid cells

Comment on: the tumour microenvironment shapes innate lymphoid cells in patients with hepatocellular carcinoma

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