Human Lung Cancer–Derived Immunosuppressive Plasmacytoid Dendritic Cells Release IL-1α in an AIM2 Inflammasome-Dependent Manner

Sorrentino, Rosalinda; Terlizzi, Michela; Crescenzo, Vincenzo Giuseppe Di; Popolo, Ada; Pecoraro, Michela; Perillo, Giuseppe; Galderisi, Antonio; Pinto, Aldo

doi:10.1016/j.ajpath.2015.07.009

Cited by 73 publications

(88 citation statements)

References 34 publications

(64 reference statements)

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“…Previous studies have shown that AIM2 was differently expressed and functioned as both a tumor suppressor and oncogene in human cancers. AIM2 was overexpressed in nonsmall cell lung cancer and facilitated cell proliferation (Kong et al ., 2015; Sorrentino et al ., 2015). AIM2 restoration in colorectal cancer cells induced the expression of invasion‐associated genes such as VIM and MCAM (Patsos et al ., 2010).…”

Section: Introductionmentioning

confidence: 99%

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Chen

Liu

et al. 2017

Molecular Oncology

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Tumor metastasis is responsible for the high mortality rates in patients with hepatocellular carcinoma (HCC). Absent in melanoma 2 (AIM2) has been implicated in inflammation and carcinogenesis, although its role in HCC metastasis remains unknown. In the present study, we show that AIM2 protein expression was noticeably reduced in HCC cell lines and clinical samples. A reduction in AIM2 was closely associated with higher serum AFP levels, vascular invasion, poor tumor differentiation, an incomplete tumor capsule and unfavorable postsurgical survival odds. In vitro studies demonstrated that AIM2 expression was modulated by hepatitis B virus X protein (HBx) at transcriptional and post‐translational levels. HBx overexpression markedly blocked the expression of AIM2 at mRNA and protein levels by enhancing the stability of Enhancer of zeste homolog 2 (EZH2). Furthermore, HBx interacted with AIM2, resulting in an increase of AIM2 degradation via ubiquitination induction. Functionally, knockdown of AIM2 enhanced cell migration, formation of cell pseudopodium, wound healing and tumor metastasis, whereas reintroduction of AIM2 attenuated these functions. The loss of AIM2 induced the activation of epithelial‐mesenchymal transition (EMT). Fibronectin 1 (FN1) was found to be a downstream effector of AIM2, with its expression reversely modulated by AIM2. Silencing of FN1 significantly halted cell migration induced by AIM2 depletion. These data demonstrate that HBx‐induced loss of AIM2 is associated with poor outcomes and facilitates HCC metastasis by triggering the EMT process. The results of the present study therefore suggest that AIM2 is a potential prognostic biomarker in hepatitis B virus‐related HCC, as well as a possible therapeutic target for tumor metastasis.

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Section: Introductionmentioning

confidence: 99%

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Chen

Liu

et al. 2017

Molecular Oncology

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“…Studies have suggested that AIM2–dependent release of alarmins promotes tumorigenesis . Increased production of IL‐1α from immunosuppressive tumor‐associated plasmacytoid dendritic cells (pDCs) in lung cancer depends on the AIM2 inflammasome . Disrupted mitochondrial iron metabolism in the absence of the mitophagy proteins PINK1 and PARK2 induces AIM2‐dependent high mobility group box 1 release in pancreatic ductal adenocarcinoma, promoting the upregulation of immune checkpoint protein programmed cell death ligand 1 .…”

Section: Role Of Aim2 In Sterile Inflammatory Diseasesmentioning

confidence: 99%

Role of AIM2 inflammasome in inflammatory diseases, cancer and infection

2019

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AIM2 is a cytosolic innate immune receptor which recognizes double-stranded DNA (dsDNA) released during cellular perturbation and pathogenic assault. AIM2 recognition of dsDNA leads to the assembly of a large multiprotein oligomeric complex termed the inflammasome. This inflammasome assembly leads to the secretion of bioactive interleukin-1β (IL-1β) and IL-18 and induction of an inflammatory form of cell death called pyroptosis. Sensing of dsDNA by AIM2 in the cytosol is crucial to mediate protection against the invading pathogens including bacteria, virus, fungi and parasites. AIM2 also responds to dsDNA released from damaged host cells, resulting in the secretion of the effector cytokines thereby driving the progression of sterile inflammatory diseases such as skin disease, neuronal disease, chronic kidney disease, cardiovascular disease and diabetes. Additionally, the protection mediated by AIM2 in the development of colorectal cancer depends on its ability to regulate epithelial cell proliferation and gut microbiota in maintaining intestinal homeostasis independently of the effector cytokines. In this review, we will highlight the recent progress on the role of the AIM2 inflammasome as a guardian of cellular integrity in modulating chronic inflammatory diseases, cancer and infection.Keywords: AIM2 r cell death r gasdermin r inflammasome r pyroptosis

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“…For instance, in ovarian cancer, pDCs modulate neo-angiogenesis via TNF-α and IL-8 production upon CD40L activation [139]. Recently, it has been demonstrated that TA-pDCs produce the pro-angiogenic and pro-invasive cytokine IL-1α in an AIM2-dependent manner, and promote tumor cell proliferation and angiogenesis in NSCLC [182]. Finally, the secretion of GrB could be an additional tolerogenic mechanism of pDCs [97,99].…”

Section: The Dual Role Of Pdcs In Human Cancermentioning

confidence: 99%

Human Plasmacytoid Dendritic Cells and Cutaneous Melanoma

Monti

Consoli

Vescovi

et al. 2020

Cells

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The prognosis of metastatic melanoma (MM) patients has remained poor for a long time. However, the recent introduction of effective target therapies (BRAF and MEK inhibitors for BRAFV600-mutated MM) and immunotherapies (anti-CTLA-4 and anti-PD-1) has significantly improved the survival of MM patients. Notably, all these responses are highly dependent on the fitness of the host immune system, including the innate compartment. Among immune cells involved in cancer immunity, properly activated plasmacytoid dendritic cells (pDCs) exert an important role, bridging the innate and adaptive immune responses and directly eliminating cancer cells. A distinctive feature of pDCs is the production of high amount of type I Interferon (I-IFN), through the Toll-like receptor (TLR) 7 and 9 signaling pathway activation. However, published data indicate that melanoma-associated escape mechanisms are in place to hijack pDC functions. We have recently reported that pDC recruitment is recurrent in the early phases of melanoma, but the entire pDC compartment collapses over melanoma progression. Here, we summarize recent advances on pDC biology and function within the context of melanoma immunity.

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Human Lung Cancer–Derived Immunosuppressive Plasmacytoid Dendritic Cells Release IL-1α in an AIM2 Inflammasome-Dependent Manner

Cited by 73 publications

References 34 publications

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Role of AIM2 inflammasome in inflammatory diseases, cancer and infection

Human Plasmacytoid Dendritic Cells and Cutaneous Melanoma

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