التفاصيل البيبلوغرافية
| العنوان: |
Adenosine Increases the Immunosuppressive Capacity of Cervical Cancer Cells by Increasing PD-L1 Expression and TGF-β Production through Its Interaction with A 2A R/A 2B R. |
| المؤلفون: |
García-Rocha, Rosario, Monroy-García, Alberto, Vázquez-Cruz, Ana Luisa, Marín-Aquino, Luis Antonio, Weiss-Steider, Benny, Hernández-Montes, Jorge, Don-López, Christian Azucena, Molina-Castillo, Gabriela, Mora-García, María de Lourdes |
| المصدر: |
Pharmaceuticals (14248247); Mar2024, Vol. 17 Issue 3, p397, 17p |
| مصطلحات موضوعية: |
CYTOTOXIC T cells, PROGRAMMED death-ligand 1, CERVICAL cancer, ADENOSINES, CANCER cells, T cells, PURINERGIC receptors, T cell receptors |
| مستخلص: |
The present study provides evidence showing that adenosine (Ado) increases the expression of programmed death ligand 1 (PD-L1) in cervical cancer (CeCa) cells by interacting with A2AR/A2BR and that TGF-β1 acts in an autocrine manner to induce PD-L1 expression, enhancing the immunosuppressive effects of CeCa cells on activated T lymphocytes (ATLs) and CD8+ cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from E6 and E7 proteins of HPV-16. Interestingly, the addition of the antagonists ZM241385 and MRS1754, which are specific for A2AR and A2BR, respectively, or SB-505124, which is a selective TGF-β1 receptor inhibitor, to CeCa cell cultures significantly inhibited PD-L1 expression. In addition, supernatants from CeCa cells that were treated with Ado (CeCa-Ado Sup) increased the expression of PD-1, TGF-β1, and IL-10 and decreased the expression of IFN-γ in ATLs. Interestingly, the addition of an anti-TGF-β neutralizing antibody strongly reversed the effect of CeCa-Ado Sup on PD-1 expression in ATLs. These results strongly suggest the presence of a feedback mechanism that involves the adenosinergic pathway, the production of TGF-β1, and the upregulation of PD-L1 expression in CeCa cells that suppresses the antitumor response of CTLs. The findings of this study suggest that this pathway may be clinically important and may be a therapeutic target. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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