Thymic Stromal Lymphopoietin and Cancer: Th2-Dependent and -Independent Mechanisms

Protti, Maria Pia; Monte, Lucia De

doi:10.3389/fimmu.2020.02088

Cited by 30 publications

(26 citation statements)

References 67 publications

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“…The interaction between a non-IgE-mediated stimulus, such as LPS, T H 2 cytokines and TSLP in human lung macrophages greatly extend the potential proinflammatory roles of TSLP in inflammatory lung disorders. The relevance of TSLP-dependent T H 2 inflammation in allergic disorders and in cancer has been recently emphasized [2,28].…”

Section: Discussionmentioning

confidence: 99%

“…The plethora of immune cell types that can either produce or respond to TSLP emphasizes the importance of this cytokine in multiple biological processes [1,2]. A novel and unexpected function of TSLP has been demonstrated in experimental and human cancers [2,28]. In particular, TSLP has been linked to the progression of several experimental [29][30][31][32][33] and human tumors [33][34][35][36][37][38][39][40][41][42][43][44][45][46].…”

Section: Introductionmentioning

confidence: 99%

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Human Lung-Resident Macrophages Express and Are Targets of Thymic Stromal Lymphopoietin in the Tumor Microenvironment

Braile

Fiorelli

Sorriento

et al. 2021

Cells

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Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine highly expressed by epithelial cells and several innate and adaptive immune cells. TSLP exerts its biological effects by binding to a heterodimeric complex composed of TSLP receptor (TSLPR) and IL-7Rα. In humans, there are two TSLP isoforms: the short form (sfTSLP), constitutively expressed, and the long form (lfTSLP), which is upregulated in inflammation. TSLP has been implicated in the induction and progression of several experimental and human cancers. Primary human lung macrophages (HLMs), monocyte-derived macrophages (MDMs), and peripheral blood monocytes consitutively expressed sfTSLP mRNA. Incubation of HLMs, MDMs, and monocytes with lipopolysaccharide (LPS) or IL-4, but not with IL-13, induced TSLP release from HLMs. LPS, but not IL-4 or IL-13, induced CXCL8 release from HLMs. LPS, IL-4 alone or in combination with IL-13, induced the expression of lfTSLP, but not of sfTSLP from HLMs. Preincubation of HLMs with IL-4, alone or in combination with IL-13, but not IL-13 alone, synergistically enhanced TSLP release from LPS-activated macrophages. By contrast, IL-4, alone or in combination with IL-13, inhibited LPS-induced CXCL8 release from HLMs. Immunoreactive TSLP was detected in lysates of HLMs, MDMs, and monocytes. Incubation of HLMs with TSLP induced the release of proinflammatory (TNF-α), angiogenic (VEGF-A, angiopoietin 2), and lymphangiogenic (VEGF-C) factors. TSLP, TSLPR, and IL-7Rα were expressed in intratumoral and peritumoral areas of human lung cancer. sfTSLP and lfTSLP mRNAs were differentially expressed in peritumoral and intratumoral lung cancer tissues. The TSLP system, expressed in HLMs, MDMs, and monocytes, could play a role in chronic inflammatory disorders including lung cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Lung-Resident Macrophages Express and Are Targets of Thymic Stromal Lymphopoietin in the Tumor Microenvironment

Braile

Fiorelli

Sorriento

et al. 2021

Cells

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“…Our results suggest possible mechanisms by which IER5 regulates the infiltration of Th2 cells, along with γδ T cells in glioma patients. Th2 cytokines such as IL-4, IL-10, IL-5, IL-9, and IL-6 can down-regulate tumor-specific immunity (Protti and De Monte, 2020). These cytokines along with their receptors were highly expressed in glioblastoma samples and cell lines (Hao et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

High IER5 Gene Expression Is Associated With Poor Prognosis in Glioma Patients

Wang

Zeng

et al. 2021

Front. Cell Dev. Biol.

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ObjectiveImmediate early response 5 (IER5) plays a core role in cell cycle and response to irradiation. However, its role in glioma remains unclear. We aimed to evaluate its prognostic significance in glioma based on The Cancer Genome Atlas data resource.MethodsThe Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were employed to explore the relationship between IER5 expression and clinicopathological features. Kaplan–Meier and Cox regression analyses were implemented to investigate the relationship of IER5 with prognosis. A nomogram to estimate the impact of IER5 on prognosis was created based on the Cox multivariate data. We performed gene set enrichment analysis (GSEA) to determine the key signaling cascades associated with IER5. Immunohistochemistry was performed to examine IER5 expression in a tissue microarray (TMA) of glioma samples.ResultsImmediate early response 5 gene expression was elevated in glioma patients. The level of IER5 was significantly correlated with WHO grade [OR = 6.71 (4.34–10.68) for G4 vs. G2 and G3], IDH (isocitrate dehydrogenase enzyme) status [OR = 13.35 (8.92–20.46) for wild-type (WT) vs. mutated (Mut)], epidermal growth factor receptor status [OR = 8.42 (4.32–18.43) for Mut vs. WT], age [OR = 0.27 (0.18–0.41) for ≤ 60 years vs. >60 years], and histological type [OR = 7.13 (4.63–11.31] for glioblastoma vs. astrocytoma, oligoastrocytoma, and oligodendroglioma). Univariate analyses revealed that high IER5 expression was linked to short overall survival (OS) [hazard ratio (HR): 3.747; 95% confidence interval (CI): 2.847–4.933; and P < 0.001]. High IER5 expression was linked to poor OS in multivariate analyses (HR: 2.474; 95% CI: 1.552–3.943; and P < 0.001). TMA results showed that high IER5 protein levels were related to short OS (HR: 1.84; 95% CI: 1.10–3.07; and P = 0.021) and poor disease-specific survival (HR: 1.82; 95% CI: 1.09–3.04; and P = 0.023). GSEA showed that many tumor related pathways were enriched differentially in the IER5-high expression group. The C-index and calibration plots of the nomogram showed an effective estimation performance in glioma patients.ConclusionHerein, we established that IER5 plays a critical role in glioma progression and prognosis, which might be an important biomarker for the prognosis of glioma patients.

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“…Our results showed that Th2 and mast cells were significantly infiltrated in gastric cancer patients. Strong infiltration by Th2 cells may be associated with early carcinogenesis and promote the activation of a tumor microenvironment that favors angiogenesis and metastasis [ 33 ]. Studies have shown that Th2 cell responses are associated with the development and progression of human gastric cancer [ 34 ].…”

Section: Discussionmentioning

confidence: 99%