Induction of specific T helper-9 cells to inhibit glioma cell growth

Zheng, Haiyan; Yang, Baohua; Xu, Dedong; Wang, Wenbo; Tan, Jie; Sun, Liyuan; Li, Qinghua; Sun, Li; Xia, Xuewei

doi:10.18632/oncotarget.13981

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…Glioma is a common brain malignancy, accounting for about 50% of primary brain tumors [ 10 ]. Glioma refers to all neuroepithelial-derived tumors in a broad sense; and in a narrow sense, it refers to tumors derived from glial cells.…”

Section: Introductionmentioning

confidence: 99%

γδ T Cells in Peripheral Blood of Glioma Patients

et al. 2018

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BackgroundGlioma is a common brain malignancy, but the effects of the γδ T cells and their subsets in peripheral blood in patients with glioma have not been reported.Material/MethodsFlow cytometry was used to analyze the functions and expressions of δ T cells and their subsets in peripheral blood in healthy controls and patients with glioma. The Vδ2 T cells and the activation of killing function-related signaling pathway were analyzed by Western blot assay; the immunosuppressive functions of Vδ1 T cells were detected by CFSE proliferation assay; and the Vδ2 T cell killing functions were detected by killing assay.ResultsCompared with the healthy controls, the ratio of Vδ1 T cells was significantly increased and the ratio of Vδ2 T cells was significantly decreased. After in vitro culture and anti-TCR γδ antibody stimulation and in the presence of IL-2, in the patients with glioma, the Vδ1 T cells dominated and Vδ2 T cells were scarce. Flow cytometry staining showed that expression of immunosuppression-related molecules on the Vδ1 T cell surface was significantly increased, while the expression of killing function-related molecules and the activation of killing function-related signaling pathway in the Vδ2 T cells were significantly decreased. Functional test results showed that the immunosuppressive function of Vδ1T cells was enhanced and the killing function of Vδ1T cells was reduced.ConclusionsThe ratio and function changes of Vδ1 T cells and Vδ2 T cells are possibly associated with the pathogenesis of glioma.

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Section: Introductionmentioning

confidence: 99%

γδ T Cells in Peripheral Blood of Glioma Patients

et al. 2018

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“…Purwar et al [ 10 ] demonstrated that IL-9 depletion in RORγt -deficient mice promoted melanoma growth. Zheng et al [ 64 ] demonstrated that Th9 cells produce IL-9 to induce glioma cell apoptosis and inhibit tumor growth. Interestingly, tumor-specific Th9 cells displayed a unique PU.1-TRAF6-NF-kB activation–driven hyperproliferative feature, suggesting a persistence mechanism rather than an antiapoptotic strategy.…”

Section: Discussionmentioning

confidence: 99%

The Differentially Expressed Genes Responsible for the Development of T Helper 9 Cells From T Helper 2 Cells in Various Disease States: Immuno-Interactomics Study

Khokhar¹,

Purohit²,

Gadwal³

et al. 2023

JMIR Bioinform Biotech

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Background T helper (Th) 9 cells are a novel subset of Th cells that develop independently from Th2 cells and are characterized by the secretion of interleukin (IL)-9. Studies have suggested the involvement of Th9 cells in variable diseases such as allergic and pulmonary diseases (eg, asthma, chronic obstructive airway disease, chronic rhinosinusitis, nasal polyps, and pulmonary hypoplasia), metabolic diseases (eg, acute leukemia, myelocytic leukemia, breast cancer, lung cancer, melanoma, pancreatic cancer), neuropsychiatric disorders (eg, Alzheimer disease), autoimmune diseases (eg, Graves disease, Crohn disease, colitis, psoriasis, systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, atopic dermatitis, eczema), and infectious diseases (eg, tuberculosis, hepatitis). However, there is a dearth of information on its involvement in other metabolic, neuropsychiatric, and infectious diseases. Objective This study aims to identify significant differentially altered genes in the conversion of Th2 to Th9 cells, and their regulating microRNAs (miRs) from publicly available Gene Expression Omnibus data sets of the mouse model using in silico analysis to unravel various pathogenic pathways involved in disease processes. Methods Using differentially expressed genes (DEGs) identified from 2 publicly available data sets (GSE99166 and GSE123501) we performed functional enrichment and network analyses to identify pathways, protein-protein interactions, miR-messenger RNA associations, and disease-gene associations related to significant differentially altered genes implicated in the conversion of Th2 to Th9 cells. Results We extracted 260 common downregulated, 236 common upregulated, and 634 common DEGs from the expression profiles of data sets GSE99166 and GSE123501. Codifferentially expressed ILs, cytokines, receptors, and transcription factors (TFs) were enriched in 7 crucial Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology. We constructed the protein-protein interaction network and predicted the top regulatory miRs involved in the Th2 to Th9 differentiation pathways. We also identified various metabolic, allergic and pulmonary, neuropsychiatric, autoimmune, and infectious diseases as well as carcinomas where the differentiation of Th2 to Th9 may play a crucial role. Conclusions This study identified hitherto unexplored possible associations between Th9 and disease states. Some important ILs, including CCL1 (chemokine [C-C motif] ligand 1), CCL20 (chemokine [C-C motif] ligand 20), IL-13, IL-4, IL-12A, and IL-9; receptors, including IL-12RB1, IL-4RA (interleukin 9 receptor alpha), CD53 (cluster of differentiation 53), CD6 (cluster of differentiation 6), CD5 (cluster of differentiation 5), CD83 (cluster of differentiation 83), CD197 (cluster of differentiation 197), IL-1RL1 (interleukin 1 receptor-like 1), CD101 (cluster of differentiation 101), CD96 (cluster of differentiation 96), CD72 (cluster of differentiation 72), CD7 (cluster of differentiation 7), CD152 (cytotoxic T lymphocyte–associated protein 4), CD38 (cluster of differentiation 38), CX3CR1 (chemokine [C-X3-C motif] receptor 1), CTLA2A (cytotoxic T lymphocyte–associated protein 2 alpha), CTLA28, and CD196 (cluster of differentiation 196); and TFs, including FOXP3 (forkhead box P3), IRF8 (interferon regulatory factor 8), FOXP2 (forkhead box P2), RORA (RAR-related orphan receptor alpha), AHR (aryl-hydrocarbon receptor), MAF (avian musculoaponeurotic fibrosarcoma oncogene homolog), SMAD6 (SMAD family member 6), JUN (Jun proto-oncogene), JAK2 (Janus kinase 2), EP300 (E1A binding protein p300), ATF6 (activating transcription factor 6), BTAF1 (B-TFIID TATA-box binding protein associated factor 1), BAFT (basic leucine zipper transcription factor), NOTCH1 (neurogenic locus notch homolog protein 1), GATA3 (GATA binding protein 3), SATB1 (special AT-rich sequence binding protein 1), BMP7 (bone morphogenetic protein 7), and PPARG (peroxisome proliferator–activated receptor gamma, were able to identify significant differentially altered genes in the conversion of Th2 to Th9 cells. We identified some common miRs that could target the DEGs. The scarcity of studies on the role of Th9 in metabolic diseases highlights the lacunae in this field. Our study provides the rationale for exploring the role of Th9 in various metabolic disorders such as diabetes mellitus, diabetic nephropathy, hypertensive disease, ischemic stroke, steatohepatitis, liver fibrosis, obesity, adenocarcinoma, glioblastoma and glioma, malignant neoplasm of stomach, melanoma, neuroblastoma, osteosarcoma, pancreatic carcinoma, prostate carcinoma, and stomach carcinoma.

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“…21,22 Th9 cells can stimulate inflammatory responses and participate in pathophysiological processes of various immune diseases. 23,24 As the main effector of Th9 cells, IL-9 is both a growth factor on T cell and a direct effector on B cells. It can play an important role in the regulation of immunoglobulin synthesis.…”

Section: Discussionmentioning

confidence: 99%

<p>miR-145 Inhibits Th9 Cell Differentiation by Suppressing Activation of the PI3K/Akt/mTOR/p70S6K/HIF-1α Pathway in Malignant Ascites from Liver Cancer</p>

Huang

Jiang

Shi

et al. 2020

OTT

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Purpose: Our previous experiments confirmed that T helper type 9 (Th9) cells were involved in the occurrence and development of malignant ascites caused by liver cancer. The current study investigated the mechanism underlying microRNA (miR-145)-mediated inhibition of Th9 cells in an malignant ascites model with liver cancer. Materials and Methods: CD4+ T cells were induced to differentiate Th9 cells after transfection with miR-145 mimics or negative control. A malignant ascites mouse model was transfected with miR-145agomir or negative control. Th9 cells were detected by flow cytometry. Enzyme-linked immunosorbent assay was applied to detect the interleukin 9 (IL-9) cytokine and hypoxia-inducible factor 1 alpha (HIF-1α). RT-PCR was used to detect the expression of miR-145 and phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin/p70 ribosomal protein S6 kinase/HIF-1α (PI3K/Akt/mTOR/p70S6K/HIF-1α) mRNA. Western blotting and immunofluorescence were performed to detect the expression of PI3K/Akt/mTOR/p70S6K/HIF-1α-related proteins. Results: In vitro experiments showed that miR-145 inhibited Th9 cell polarization, HIF-1α expression, and PI3K/Akt/mTOR/p70S6K pathway activation. In the malignant ascites mouse model, miR-145 also demonstrated inhibitory effects on Th9 cell differentiation through the PI3K/Akt/mTOR/p70S6K/HIF-1α pathway. Conclusion: miR-145 may inhibit Th9 cell differentiation through the PI3K/Akt/mTOR/ p70S6K/HIF-1α pathway. These findings suggest a novel therapeutic target for malignant ascites from liver cancer.

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Induction of specific T helper-9 cells to inhibit glioma cell growth

Cited by 9 publications

References 33 publications

γδ T Cells in Peripheral Blood of Glioma Patients

γδ T Cells in Peripheral Blood of Glioma Patients

The Differentially Expressed Genes Responsible for the Development of T Helper 9 Cells From T Helper 2 Cells in Various Disease States: Immuno-Interactomics Study

<p>miR-145 Inhibits Th9 Cell Differentiation by Suppressing Activation of the PI3K/Akt/mTOR/p70S6K/HIF-1α Pathway in Malignant Ascites from Liver Cancer</p>

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