Thymoma patients with or without myasthenia gravis have increased Th17 cells, IL-17 production and ICOS expression

Çebi, Merve; Çakar, Arman; Erdoğdu, Eren; Tekçe, Hacer Durmuş; Yeğen, Gülçin; Özkan, Berker; Parman, Yeşim; Direskeneli, Güher Saruhan

doi:10.1016/j.jneuroim.2023.578129

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…Increased Th17 and decreased Treg cell activity were demonstrated in TAMG [ 19 , 20 ]. HIF-1 transcriptionally activates RORγt, favoring Th17 cells while inhibiting Treg cells by targeting FOXP3 for degradation [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

“…However, there was no significant difference between these groups in the periphery [ 11 , 17 , 18 ]. Finally, an increase in IL-17-related activity and a decrease in Treg cell development have also been demonstrated in TAMG or thymoma without MG (TOMA) [ 19 , 20 ]. All these data suggest possible Treg- and IL-17-related imbalance and potential activation of Th17 cells in the thymus of MG patients [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Thymic gene expression analysis reveals a potential link between HIF-1A and Th17/Treg imbalance in thymoma associated myasthenia gravis

Altınönder,

Kaya,

Yentür

et al. 2024

J Neuroinflammation

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Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T (Treg) cells have been demonstrated in subgroups of MG. On the other hand, hypoxia-inducible factor 1 (HIF-1) has been shown to regulate the Th17/Treg balance by inducing Th17 differentiation while attenuating Treg development. To identify the underlying mechanisms of different thymic pathologies in MG development, we evaluated thymic samples from thymoma-associated myasthenia gravis (TAMG), MG with hyperplasia (TFH-MG) and thymoma without MG (TOMA) patients. Differential gene expression analysis revealed that TAMG and TFH-MG cells are associated with different functional pathways. A higher RORC/FOXP3 ratio provided evidence for Th17/Treg imbalance in TAMG potentially related to increased HIF1A. The hypoxic microenvironment in thymoma may be a driver of TAMG by increasing HIF1A. These findings may lead to new therapeutic approaches targeting HIF1A in the development of TAMG.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thymic gene expression analysis reveals a potential link between HIF-1A and Th17/Treg imbalance in thymoma associated myasthenia gravis

Altınönder,

Kaya,

Yentür

et al. 2024

J Neuroinflammation

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“…The implications of these findings on the tumor immune microenvironment have yet to be explored, though the influence of TSLP on Th17 and interleukin (IL)-17 production has been reported. Additionally, imbalances of Th17 and Treg and ICOS + CD4 + T cell frequencies in the peripheral blood have been reported in TAMG patients [78,79].…”

Section: Epigenetic Alterations and Associated Therapiesmentioning

confidence: 98%

What Have We Learned from Molecularly Informed Clinical Trials on Thymomas and Thymic Carcinomas—Current Status and Future Directions?

Maniar,

Loehrer

2024

Cancers

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Thymic epithelial tumors (TETs), which include thymomas and thymic carcinomas, are a rare, heterogeneous group of malignancies that originate from the thymus gland. As an important organ of immune cell development, thymic tumors, particularly thymomas, are often associated with paraneoplastic autoimmune disorders. The advances in targeted therapies for both solid and hematologic malignancies have resulted in improved patient outcomes, including better and more durable efficacy and improved toxicity. Targeted therapies have also been investigated in the treatment of TETs, though the results have largely been modest. These have included somatostatin-receptor-targeting therapies, KIT- and EGFR-directed tyrosine kinase inhibitors, epigenetic modulators, anti-angiogenesis agents, and agents targeting the cell proliferation and survival pathways and cell cycle regulators. Numerous investigated treatments have failed or underperformed due to a lack of a strong biomarker of efficacy. Ongoing trials are attempting to expand on previous experiences, including the exploration of effective drugs in early-stage disease. Novel combination therapy strategies are also undergoing evaluation, with the goal of augmenting efficacy and understanding the toxicity while expanding the biomarkers of efficacy and safety. With advances in technology to improve target identification and drug delivery, old targets may become new opportunities, and the subsequently developed drugs may find their place in the treatment of thymic tumors.

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“…IL-17 also plays a crucial role in the activity regulatio of T-helper 17 (Th 17) cells. Consequently, the involvement of the IL-17 family has bee implicated in numerous immune/autoimmune-related diseases including anti-tumor im munity [36,37]. 3.…”

Section: Differences In Protein Expression Of Solid Tumors In Each Groupmentioning

confidence: 99%

Systemic Immunomodulatory Effects of Codonopsis pilosula Glucofructan on S180 Solid-Tumor-Bearing Mice

Fan,

Long,

Gong

et al. 2023

IJMS

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The immune functions of the body are intricately intertwined with the onset and advancement of tumors, and immunotherapy mediated by bioactive compounds has exhibited initial effectiveness in overcoming chemotherapy resistance and inhibiting tumor growth. However, the comprehensive interpretation of the roles played by immunologic components in the process of combating tumors remains to be elucidated. In this study, the Codonopsis pilosula glucofructan (CPG) prepared in our previous research was employed as an immunopotentiator, and the impacts of CPG on both the humoral and cellular immunity of S180 tumor-bearing mice were investigated. Results showed that CPG administration of 100 mg/kg could effectively inhibit tumor growth in mice with an inhibitory ratio of 45.37% and significantly improve the expression of Interleukin-2 (IL-2), Interferon-γ (IFN-γ), and Tumor Necrosis Factor-α (TNF-α). Additionally, CPG clearly enhanced B-cell-mediated humoral immunity and immune-cell-mediated cellular immunity, and, finally, induced S180 cell apoptosis by arresting cells in the G0/G1 phase, which might result from the IL-17 signaling pathway. These data may help to improve comprehension surrounding the roles of humoral and cellular immunity in anti-tumor immune responses.

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Thymoma patients with or without myasthenia gravis have increased Th17 cells, IL-17 production and ICOS expression

Cited by 4 publications

References 36 publications

Thymic gene expression analysis reveals a potential link between HIF-1A and Th17/Treg imbalance in thymoma associated myasthenia gravis

Thymic gene expression analysis reveals a potential link between HIF-1A and Th17/Treg imbalance in thymoma associated myasthenia gravis

What Have We Learned from Molecularly Informed Clinical Trials on Thymomas and Thymic Carcinomas—Current Status and Future Directions?

Systemic Immunomodulatory Effects of Codonopsis pilosula Glucofructan on S180 Solid-Tumor-Bearing Mice

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