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Tytuł pozycji:

Breast Cancer Cell-Derived Adenosine Enhances Generation and Suppressor Function of Human Adaptive Regulatory T Cells.

Tytuł:
Breast Cancer Cell-Derived Adenosine Enhances Generation and Suppressor Function of Human Adaptive Regulatory T Cells.
Autorzy:
Mandapathil M; Department of Otorhinolaryngology, Asklepios Clinic St. Georg, 20099 Hamburg, Germany.; Department of Otorhinolaryngol Head & Neck Surg, Philipps University of Marburg, 35033 Marburg, Germany.
Szczepanski MJ; Department of Biochemistry, Medical University of Warsaw, PL-02097 Warsaw, Poland.
Jackson EK; Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Lang S; Department of Otorhinolaryngology, University of Duisburg-Essen, 45147 Essen, Germany.
Whiteside TL; UPMC Hillman Cancer Center, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Źródło:
Journal of personalized medicine [J Pers Med] 2021 Jul 30; Vol. 11 (8). Date of Electronic Publication: 2021 Jul 30.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI AG, 2011-
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Grant Information:
P30 DK079307 United States DK NIDDK NIH HHS; U01 DE029759 United States DE NIDCR NIH HHS
Contributed Indexing:
Keywords: CD73; Treg; adenosine; breast cancer (BrCa); immunosuppression
Entry Date(s):
Date Created: 20210827 Latest Revision: 20220519
Update Code:
20240104
PubMed Central ID:
PMC8401826
DOI:
10.3390/jpm11080754
PMID:
34442398
Czasopismo naukowe
Introduction: Adaptive regulatory T cells (Tr1) are induced in the periphery by environmental stimuli. CD73 expression and adenosine (ADO) production by tumor cells may influence Tr1 generation and their immunosuppressive activity.
Material and Methods: Tr1 were generated in co-cultures of CD4+CD25neg T cells, autologous immature dendritic cells (iDC), and irradiated ADO-producing CD73+ or non-producing CD73neg breast cancer (BrCa) cell lines (TU). The expression of ectonucleotidases and other surface markers on Tr1 was determined by flow cytometry. Tr1-mediated suppression of proliferation was evaluated in CFSE-based assays. Luciferase-based ATP detection assays and mass spectrometry were used to measure ATP hydrolysis and ADO levels. Cytokine levels were measured by ELISA or Luminex. CD73 expression on tumor cells or T cells in TU tissues was assessed by immunofluorescence.
Results: CD73+ TU induced higher numbers of Tr1 cells ( p < 0.01) than CD73neg TU. Tr1TU73+ hydrolyzed more exogenous ATP, produced more ADO, and mediated higher suppression than Tr1TU73neg ( p < 0.05 for all). ARL67156, an ectonucleotidase inhibitor, and ZM241385, A2A receptor antagonist, reduced suppression of proliferation mediated by Tr1TU73+ cells ( p < 0.01). Basal-like primary BrCa cells expressed higher levels of ectonucleotidases and induced more Tr1 than less aggressive primary luminal-like BrCa.
Conclusion: BrCa producing ADO (CD73+ TU) favor the induction of Tr1, which expresses CD39 and CD73, hydrolyzes ATP to ADO, and effectively suppresses anti-tumor immunity.

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