Academic Journal
Human Melanoma-Associated Mast Cells Display a Distinct Transcriptional Signature Characterized by an Upregulation of the Complement Component 3 That Correlates With Poor Prognosis
| العنوان: | Human Melanoma-Associated Mast Cells Display a Distinct Transcriptional Signature Characterized by an Upregulation of the Complement Component 3 That Correlates With Poor Prognosis |
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| المؤلفون: | Bahri, Rajia, Kiss, Orsolya, Prise, Ian, Garcia-Rodriguez, Karen M, Atmoko, Haris, Martínez-Gómez, Julia M, Levesque, Mitchell Paul, Dummer, Reinhard, Smith, Michael P, Wellbrock, Claudia, Bulfone-Paus, Silvia |
| المصدر: | Bahri, Rajia; Kiss, Orsolya; Prise, Ian; Garcia-Rodriguez, Karen M; Atmoko, Haris; Martínez-Gómez, Julia M; Levesque, Mitchell Paul; Dummer, Reinhard; Smith, Michael P; Wellbrock, Claudia; Bulfone-Paus, Silvia (2022). Human Melanoma-Associated Mast Cells Display a Distinct Transcriptional Signature Characterized by an Upregulation of the Complement Component 3 That Correlates With Poor Prognosis. Frontiers in Immunology, 13:861545. |
| بيانات النشر: | Frontiers Research Foundation |
| سنة النشر: | 2022 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Dermatology Clinic, 610 Medicine & health, Immunology, Immunology and Allergy |
| الوصف: | Cutaneous melanoma is one of the most aggressive human malignancies and shows increasing incidence. Mast cells (MCs), long-lived tissue-resident cells that are particularly abundant in human skin where they regulate both innate and adaptive immunity, are associated with melanoma stroma (MAMCs). Thus, MAMCs could impact melanoma development, progression, and metastasis by secreting proteases, pro-angiogenic factors, and both pro-inflammatory and immuno-inhibitory mediators. To interrogate the as-yet poorly characterized role of human MAMCs, we have purified MCs from melanoma skin biopsies and performed RNA-seq analysis. Here, we demonstrate that MAMCs display a unique transcriptome signature defined by the downregulation of the FcεRI signaling pathway, a distinct expression pattern of proteases and pro-angiogenic factors, and a profound upregulation of complement component C3. Furthermore, in melanoma tissue, we observe a significantly increased number of C3$^{+}$ MCs in stage IV melanoma. Moreover, in patients, C3 expression significantly correlates with the MC-specific marker TPSAB1, and the high expression of both markers is linked with poorer melanoma survival. In vitro, we show that melanoma cell supernatants and tumor microenvironment (TME) mediators such as TGF-β, IL-33, and IL-1β induce some of the changes found in MAMCs and significantly modulate C3 expression and activity in MCs. Taken together, these data suggest that melanoma-secreted cytokines such as TGF-β and IL-1β contribute to the melanoma microenvironment by upregulating C3 expression in MAMCs, thus inducing an MC phenotype switch that negatively impacts melanoma prognosis. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1664-3224 |
| Relation: | https://www.zora.uzh.ch/id/eprint/220002/1/ZORA_pdf.pdf; info:pmid/35669782; urn:issn:1664-3224 |
| DOI: | 10.3389/fimmu.2022.861545 |
| الاتاحة: | https://www.zora.uzh.ch/id/eprint/220002/ https://www.zora.uzh.ch/id/eprint/220002/1/ZORA_pdf.pdf https://doi.org/10.3389/fimmu.2022.861545 |
| Rights: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.E883F4F6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16643224 |
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| DOI: | 10.3389/fimmu.2022.861545 |