Tumor-promoting effect of IL-23 in mammary cancer mediated by infiltration of M2 macrophages and neutrophils in tumor microenvironment

Nie, Wen; Takata, Yasuyuki; Sang, Yaxiong; Gao, Xiang

doi:10.1016/j.bbrc.2016.12.048

Cited by 56 publications

(42 citation statements)

References 37 publications

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“…; Nie et al. ) Also in a model of experimental autoimmune uveitis, it was found that IL‐23 receptor expressing γδ T cells can exert immune‐suppressive effects due to their ability to bind IL‐23. (Liang et al.…”

Section: Discussionmentioning

confidence: 99%

Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age‐related macular degeneration, glaucoma and cataract

Berge

Fazil

Born

et al. 2018

Acta Ophthalmologica

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Purpose To analyse intraocular cytokine levels and prevalence of intraocular antiretinal antibodies (ARAs) in patients with retinitis pigmentosa (RP), age‐related macular degeneration (AMD), glaucoma and cataract, and correlate the results to clinical manifestations. Methods We collected intraocular fluid samples from patients with RP (n = 25), AMD (n = 12), glaucoma (n = 28) and cataract (n = 22), and serum samples paired with the intraocular fluids from patients with RP (N = 7) and cataract (n = 10). Interleukin (IL)‐1β, IL‐1ra, IL‐2, IL‐6, IL‐6rα, IL‐7, IL‐8, IL‐10, IL‐17A, IL‐23, thymus‐ and activation‐regulated chemokine (TARC), monocyte chemoattractant protein‐1 (MCP‐1), tumour necrosis factor‐alpha (TNF‐α), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) were measured using a multiplex assay. Antiretinal antibodies (ARA) detection was performed by indirect immunofluorescence. Results Increasing age was associated with increasing levels of IL‐6, IL‐8, TNF‐α and VEGF. All patient groups exhibited distinct profiles of intraocular cytokines. Intraocular levels of IL‐8 were highest in patients with AMD and glaucoma. Cataract patients exhibited high intraocular levels of IL‐23. Intraocular levels of IL‐2, IL‐6, MCP‐1 and PlGF in RP patients exceeded the levels of serum, indicating intraocular production. Intraocular ARAs were found in only one patient with AMD. Conclusion Increased levels of inflammatory cytokines in intraocular fluid of patients with originally noninflammatory ocular diseases show that intraocular inflammation is involved in their pathogenesis of these entities. Moreover, we show that increasing age is associated with increasing levels of intraocular cytokines and conclude that future studies on intraocular mediators should be corrected for age of patients.

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Section: Discussionmentioning

confidence: 99%

Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age‐related macular degeneration, glaucoma and cataract

Berge

Fazil

Born

et al. 2018

Acta Ophthalmologica

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Section: Discussionmentioning

confidence: 99%

“…IL-23 plays an important role in inducing Th17 cell proliferation as well as in the angiogenesis of tumors [3][4][5][6][7]. Indeed, Nie et al [4] reported that IL-23 promotes the recruitment of M2 macrophages and neutrophils, which secrete immunosuppressive cytokines and vascular endothelial growth factor as well as matrix metalloproteinase 9 (MMP9) into tumor tissues. Since tumor-associated macrophages and tumor-associated neutrophils are significant components of the microenvironment of solid tumors in the majority of cancers [8,9], IL-23 could be one of the crucial factors for the progression of cancers, including skin cancers.…”

Section: Discussionmentioning

confidence: 99%

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

et al. 2020

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Stewart-Treves syndrome (STS) is a rare cutaneous lymphangiosarcoma developing from chronic lymph edema as a consequence of radical mastectomy or surgical invasion of the groin for the treatment of cervical or penile cancer. Previous reports suggested possible mechanisms in the development of lymphangiosarcoma that correlate with the immunological background of STS patients. In this report, we described two cases of STS developing in patients who underwent radical dissection for cervical cancer, we employed immunohistochemical staining of IL-23 and IL-17. Case ReportCase 1 A 79-year-old Japanese woman visited our outpatient clinic with a 1-month history of a red, easy to bleed, nodule on the right femur. She had undergone resection of a cervical cancer 24 years before and developed prominent lymph edema in the lower extremities. During her initial visit, physical examination revealed a dark-red nodule with extended purpura on the right femur together with prominent lymph edema (Fig. 1a). Histologically, these were irregularly anastomosing vascular channels lined by single layers of enlarged, atypical endothelial cells that existed between the collagen bundles (Fig. 1b). Immunohistochemical staining revealed that these atypical endothelial cells were positive for vimentin, CD31, CD34, D2-40, and Factor VIII. The Ki67 score was 90%. Moreover, a substantial number of IL-23-producing cells (Fig. 1c) as well as IL-17-producing cells (Fig. 1d) were detected at the edge of the tumor mass. Positron emission tomography scans showed no evidence of metastases. From the

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“…Interestingly, irradiated fibroblasts can recover IL-23 secretion from irradiated dendritic cells through COX2-dependent PGE2 release [41]. Furthermore, previous studies showed that IL-23 increased the abundances of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on endothelial cells, and improved the endothelial marker CD31 in mammary cancer [42, 43]. In contrast, our findings reveal no significant difference in fibroblast and endothelial cells between indicated treatments, no matter if IL-23 treatment or irradiation, in xenograft models (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-23 receptor signaling mediates cancer dormancy and radioresistance in human esophageal squamous carcinoma cells via the Wnt/Notch pathway

Zhou

Zhu

et al. 2018

J Mol Med

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In the tumor microenvironment, inflammatory cells and molecules influence almost every process; among them, interleukin-23 (IL-23) is a pro-inflammatory molecule that exhibits pro- or anti-tumor properties, but both activities remain poorly understood. In this study, we investigated the effect of extracellular IL-23 in IL-23 receptor-positive (IL-23R+) esophageal squamous cell carcinoma (ESCC) and explored the mechanisms underlying this effect. We analyzed ESCC tumor tissues by immunohistochemical and immunofluorescence staining and found that IL-23, which was highly expressed, co-localized with Oct-4A in IL-23R+ ESCC cells. In addition, IL-23 treatment significantly increased the accumulation of CD133+ cells and activated the Wnt and Notch signaling pathways in CD133−IL-23R+ ESCC cell lines. Consistently, CD133−IL-23R+ cells pretreated with IL-23 showed stronger anti-apoptosis activity when exposed to radiation and higher survival than untreated groups. Moreover, the inhibition of Wnt/Notch signaling by a small-molecule inhibitor or siRNA abolished the effect of IL-23-induced dormancy and consequent radioresistance. Taken together, these results suggested that IL-23 facilitates radioresistance in ESCC by activating Wnt/Notch-mediated G0/1 phase arrest, and attenuating these detrimental changes by blocking the formation of dormancy may prove to be an effective pretreatment for radiotherapy.Key messages IL-23/IL-23R is correlated with the acquisition of stem-like potential in ESCC.CD133−IL-23R+ ESCCs acquired dormancy via IL-23.Radioresistance depends on IL-23-mediated Wnt/Notch pathway activation in vitro and vivo. Electronic supplementary materialThe online version of this article (10.1007/s00109-018-1724-8) contains supplementary material, which is available to authorized users.

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Tumor-promoting effect of IL-23 in mammary cancer mediated by infiltration of M2 macrophages and neutrophils in tumor microenvironment

Cited by 56 publications

References 37 publications

Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age‐related macular degeneration, glaucoma and cataract

Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age‐related macular degeneration, glaucoma and cataract

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

Interleukin-23 receptor signaling mediates cancer dormancy and radioresistance in human esophageal squamous carcinoma cells via the Wnt/Notch pathway

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