دورية أكاديمية
أعرض في EDS

Blockade of CD73 delays glioblastoma growth by modulating the immune environment.

التفاصيل البيبلوغرافية
العنوان: Blockade of CD73 delays glioblastoma growth by modulating the immune environment.
المؤلفون: Azambuja JH; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Sarmento Leite, 245 - Prédio Principal - Room 304, Porto Alegre, RS, 90.050-170, Brazil., Schuh RS; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Michels LR; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Iser IC; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil., Beckenkamp LR; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Sarmento Leite, 245 - Prédio Principal - Room 304, Porto Alegre, RS, 90.050-170, Brazil., Roliano GG; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil., Lenz GS; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Sarmento Leite, 245 - Prédio Principal - Room 304, Porto Alegre, RS, 90.050-170, Brazil., Scholl JN; Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Sévigny J; Département de Microbiologie-infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Quebec, QC, Canada.; Centre de Recherche du CHU de Québec, Université Laval, Quebec, QC, G1V 4G2, Canada., Wink MR; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Sarmento Leite, 245 - Prédio Principal - Room 304, Porto Alegre, RS, 90.050-170, Brazil.; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil., Stefani MA; Departamento de Morfologia, UFRGS, Porto Alegre, RS, Brazil., Battastini AMO; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Figueiró F; Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Teixeira HF; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Braganhol E; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Sarmento Leite, 245 - Prédio Principal - Room 304, Porto Alegre, RS, 90.050-170, Brazil. ebraganhol@ufcspa.edu.br.; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil. ebraganhol@ufcspa.edu.br.
المصدر: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2020 Sep; Vol. 69 (9), pp. 1801-1812. Date of Electronic Publication: 2020 Apr 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Verlag Country of Publication: Germany NLM ID: 8605732 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0851 (Electronic) Linking ISSN: 03407004 NLM ISO Abbreviation: Cancer Immunol Immunother Subsets: MEDLINE
أسماء مطبوعة: Publication: Berlin : Springer Verlag
Original Publication: Berlin ; New York, NY : Springer International, c1982-
مواضيع طبية MeSH: 5'-Nucleotidase/*antagonists & inhibitors , 5'-Nucleotidase/*immunology , Cell Proliferation/*physiology , Glioblastoma/*immunology , Glioblastoma/*metabolism , Glioma/*immunology , Glioma/*metabolism, Adenosine/immunology ; Adenosine/metabolism ; Animals ; Brain Neoplasms/immunology ; Brain Neoplasms/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Line, Tumor ; Immunohistochemistry/methods ; Immunotherapy/methods ; Macrophages/immunology ; Macrophages/metabolism ; Microglia/immunology ; Microglia/metabolism ; Rats
مستخلص: Immunotherapy as an approach for cancer treatment is clinically promising. CD73, which is the enzyme that produces extracellular adenosine, favors cancer progression and protects the tumor from immune surveillance. While CD73 has recently been demonstrated to be a potential target for glioma treatment, its role in regulating the inflammatory tumor microenvironment has not yet been investigated. Thus, this study explores the immunotherapeutic value of the CD73 blockade in glioblastoma. The immuno-therapeutic value of the CD73 blockade was evaluated in vivo in immunocompetent pre-clinical glioblastoma model. As such, glioblastoma-bearing rats were nasally treated for 15 days with a siRNA CD73-loaded cationic-nanoemulsion (NE-siRNA CD73R). Apoptosis was determined by flow cytometry using Annexin-V staining and cell proliferation was analyzed by Ki67 expression by immunohistochemistry. The frequencies of the CD4 + , CD8 + , and CD4 + CD25 high CD39 + (Treg) T lymphocytes; CD11b + CD45 high macrophages; CD11b + CD45 low -microglia; and CD206 + -M2-like phenotypes, along with expression levels of CD39 and CD73 in tumor and tumor-associated immune cells, were determined using flow cytometry, while inflammatory markers associated with tumor progression were evaluated using RT-qPCR. The CD73 blockade by NE-siRNA CD73 was found to induce tumor cell apoptosis. Meanwhile, the population of Tregs, microglia, and macrophages was significantly reduced in the tumor microenvironment, though IL-6, CCL17, and CCL22 increased. The treatment selectively decreased CD73 expression in the GB cells as well as in the tumor-associated-macrophages/microglia. This study indicates that CD73 knockdown using a nanotechnological approach to perform nasal delivery of siRNA-CD73 to CNS can potentially regulate the glioblastoma immune microenvironment and delay tumor growth by inducing apoptosis.
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معلومات مُعتمدة: 422298/2016-6 Conselho Nacional de Desenvolvimento Científico e Tecnológico; 310846/2014-5 Conselho Nacional de Desenvolvimento Científico e Tecnológico; 16/2551-0000265-7 Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul; 16/2551-0000473-0 Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
فهرسة مساهمة: Keywords: Ecto-5′-nucleotidase/CD73; Glioblastoma; Immunotherapy; Macrophages; Microglia; T regulatory lymphocytes
المشرفين على المادة: EC 3.1.3.5 (5'-Nucleotidase)
K72T3FS567 (Adenosine)
تواريخ الأحداث: Date Created: 20200501 Date Completed: 20200817 Latest Revision: 20240426
رمز التحديث: 20240426
مُعرف محوري في PubMed: PMC11027675
DOI: 10.1007/s00262-020-02569-w
PMID: 32350590
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-0851
DOI:10.1007/s00262-020-02569-w