Interleukin-22 promotes lung cancer cell proliferation and migration via the IL-22R1/STAT3 and IL-22R1/AKT signaling pathways

Bi, Yi; Cao, Jingyan; Shi, Jin; Lv, Li; Li, Qi; Liu, Fang; Geng, Jianxiong; Yu, Yan

doi:10.1007/s11010-016-2663-8

Cited by 31 publications

(43 citation statements)

References 35 publications

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“…Lung cancer cell lines also exhibited enhanced invasive capacity and survival, which was linked to higher activation of STAT3 and AKT. Knockdown of IL22Ra1 abolished this survival advantage . Genetic linkage analysis found SNPs in the IL22 locus that correlated with NSCLC.…”

Section: Il‐22 and Cancermentioning

confidence: 94%

A catch‐22: Interleukin‐22 and cancer

2018

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Barrier surfaces of multicellular organisms are in constant contact with the environment and infractions to the integrity of epithelial surfaces is likely a frequent event. Interestingly, components of the immune system, that can be activated by environmental compounds such as the microbiota or nutrients, are interspersed among epithelial cells or directly underlie the epithelium. It is now appreciated that immune cells continuously receive and integrate signals from the environment. Curiously, such continuous reception of stimulation does not normally trigger an inflammatory response but mediators produced by immune cells in response to such signals seem to rather promote barrier integrity and repair. The molecular mediators involved in this process are poorly understood. In recent years, the cytokine interleukin-22, produced mainly by group 3 innate lymphoid cells (ILCs), has been studied as a paradigm for how immune cells can control various aspects of epithelial cell function because expression of its receptor is restricted to non-hematopoietic cells. We will summarize here the diverse roles of IL-22 for the malignant transformation of epithelial cells, for tumor growth, wound healing and tissue repair. Furthermore, we will discuss IL-22 as a potential therapeutic target. Keywords:Aryl hydrocarbon receptor r Cancer r IL-22 r Innate lymphoid cells r RORγt IntroductionBarrier organs like the skin, the gut and lung mucosae are in constant contact with the environment. Their cellular components need to adapt to the continuous and ever changing presence of a large number of microbes (i.e., bacteria, fungi, viruses and parasites collectively referred to as the "microbiome") and their metabolites, including toxins. In addition, the epithelial barrier of the intestine is also subjected to food components, some of which are toxic by being poisonous, noxious or irritating. The skin barrier is exposed to UV irradiation, which is beneficial (e.g., conversion of Vitamin D) but can also be harmful (e.g., direct and Correspondence: Dr. Andreas Diefenbach e-mail: andreas.diefenbach@charite.de indirect DNA damage). Thus, barrier surfaces with the environment are sites where adaptive processes are initiated. Over millions of years of co-evolution of multicellular organisms with their habitat, adaptive signaling networks have been selected that are believed to shield the organism against such continuous threats and, thereby, shape their fitness. A well-studied example of such adaptive processes is microbiota-host relationships [1]. Through contact with microbial communities, epithelial function is being modified as to minimize damage to the barrier. For example, epithelial cells directly receive signals from the microbiota leading to the production of anti-bacterial proteins and to the protection of epithelial cells against TNF-triggered apoptosis [2][3][4]. * These authors contributed equally to this work.C 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 16Pedro Hernandez et al. Eur. J. Immunol. 2018. 48: ...

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Section: Il‐22 and Cancermentioning

confidence: 94%

A catch‐22: Interleukin‐22 and cancer

2018

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“…Among these, the percentage of T helper 17 (Th17) cells and related cytokine interleukin 17 (IL-17) were increased in patients with extensive tumor invasion [57][58][59]. In addition, another cytokine IL-22, produced by Th17 cells, enhanced the migration and invasion in NSCLC cell lines [60]. These results suggest that Th17 cells may be significantly correlated with the invasive potential of lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 96%

Glycomic Signatures of Plasma IgG Improve Preoperative Prediction of the Invasiveness of Small Lung Nodules

et al. 2019

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Preoperative assessment of tumor invasiveness is essential to avoid overtreatment for patients with small-sized ground-glass nodules (GGNs) of 10 mm or less in diameter. However, it is difficult to determine the pathological state by computed tomography (CT) examination alone. Aberrant glycans has emerged as a tool to identify novel potential disease biomarkers. In this study, we used a lectin microarray-based strategy to investigate whether glycosylation changes in plasma immunoglobulin G (IgG) provide additional information about the invasiveness of small GGNs before surgery. Two independent cohorts (discovery set, n = 92; test set, n = 210) of GGN patients were used. Five of 45 lectins (Sambucus nigra agglutinin, SNA; Datura stramonium agglutinin, DSA; Galanthus nivalis agglutinin, GNA; Euonymus europaeus lectin, EEL; and Vicia villosa agglutinin, VVA) were identified as independent factors associated with pathological invasiveness of small GGNs (p < 0.01). Receiver-operating characteristic (ROC) curve analysis indicated the combination of these five lectins could significantly improve the accuracy of CT in diagnosing invasive GGNs, with an area under the curve (AUC) of 0.792 (p < 0.001), a sensitivity of 74.6%, and specificity of 74.4%, which was superior to current clinical biomarkers. These results suggest that the multilectin assay based on plasma IgG glycosylation may be a useful in vitro complementary test to enhance preoperative determination of the invasiveness of GGNs and guide surgeons to select proper clinical management to avoid overtreatment.

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“…IL-22 itself has been shown to promote cellular proliferation in NSCLC cell lines [70], and indeed confirmation that IL-22 was both upregulated and pro-proliferative in NSCLC came from a recent study which demonstrated that the proliferative response was driven through the Il-22R1 receptor via either STAT3 or AKT signalling [73]. We and others, have also demonstrated that IL-22R1 was overexpressed in NSCLC [42,43], and analysis of IL-22R1expression in n=1,926 patients linked high expression of the receptor to poor prognosis [43].…”

Section: Activated T Cells Including T Helper 22 (Th22) Cells Th17 mentioning

confidence: 89%

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

Joerger

Finn

Cuffe

et al. 2016

Expert Opinion on Therapeutic Targets

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There is strong pharmaceutical development of agents targeting the IL-17-TH17 pathway for the treatment of psoriasis (Ps) and psoriatic arthritis (PsA). Lung cancer accounts for 28% of all cancer-related deaths worldwide, and roughly 80% of patients with newly-diagnosed non-small cell lung cancer (NSCLC) present with metastatic disease, with a poor prognosis of around 12 months. Therefore, there is a high unmet medical need for the development of new and potent systemic treatments in this deadly disease. The emergence of immunotherapies such as anti-PD-1 or anti-PDL1 as candidate therapies in non-small cell lung cancer (NSCLC) indicates that targeting critical immuno-modulatory cytokines including those within the IL-17-Th1/Th17 axis may have proven benefit in the treatment of lung cancer. Areas covered: In this review we describe the current evidence for aberrant IL-17-Th1/Th17 settings in cancer, particularly with regard to targeting this axis in NSCLC. We further discuss the current agents under pharmaceutical development which could potentially target this axis, and discuss the current limitations and areas of concern regarding the use of these in lung cancer. Expert opinion: Current evidence suggests that moving forward agents targeting the IL-17-Th1/Th17 pathway may have novel new oncoimmunology indications in the treatment paradigm for NSCLC.

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Interleukin-22 promotes lung cancer cell proliferation and migration via the IL-22R1/STAT3 and IL-22R1/AKT signaling pathways

Cited by 31 publications

References 35 publications

A catch‐22: Interleukin‐22 and cancer

A catch‐22: Interleukin‐22 and cancer

Glycomic Signatures of Plasma IgG Improve Preoperative Prediction of the Invasiveness of Small Lung Nodules

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

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