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| Main Authors: | , , , , , , , , , , , |
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| Format: | Artículo Open Access |
| Published: |
Wiley
2024
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| Online Access: | https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/cbf.4010 |
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- Adenosine increases PD‐L1 expression in mesenchymal stromal cells derived from cervical cancer through its interaction with A2AR/A2BR and the production of TGF‐β1 Luis Antonio Marín‐Aquino María de Lourdes Mora‐García Martha C. Moreno‐Lafont Rosario García‐Rocha Juan José Montesinos‐Montesinos Ruben López‐Santiago Luvia Enid Sánchez‐Torres Daniela Berenice Torres‐Pineda Benny Weiss‐Steider Jorge Hernández‐Montes Christian Azucena Don‐López Alberto Monroy‐García Cell Biochemistry and Function AbstractMesenchymal stromal cells (MSCs) together with malignant cells present in the tumor microenvironment (TME), participate in the suppression of the antitumor immune response through the production of immunosuppressive factors, such as transforming growth factor beta 1 (TGF‐β1). In previous studies, we reported that adenosine (Ado), generated by the adenosinergic activity of cervical cancer (CeCa) cells, induces the production of TGF‐β1 by interacting with A2AR/A2BR. In the present study, we provide evidence that Ado induces the production of TGF‐β1 in MSCs derived from CeCa tumors (CeCa‐MSCs) by interacting with both receptors and that TGF‐β1 acts in an autocrine manner to induce the expression of programmed death ligand 1 (PD‐L1) in CeCa‐MSCs, resulting in an increase in their immunosuppressive capacity on activated CD8+ T lymphocytes. The addition of the antagonists ZM241385 and MRS1754, specific for A2AR and A2BR, respectively, or SB‐505124, a selective TGF‐β1 receptor inhibitor, in CeCa‐MSC cultures significantly inhibited the expression of PD‐L1. Compared with CeCa‐MSCs, MSCs derived from normal cervical tissue (NCx‐MSCs), used as a control and induced with Ado to express PD‐L1, showed a lower response to TGF‐β1 to increase PD‐L1 expression. Those results strongly suggest the presence of a feedback mechanism among the adenosinergic pathway, the production of TGF‐β1, and the induction of PD‐L1 in CeCa‐MSCs to suppress the antitumor response of CD8+ T lymphocytes. The findings of this study suggest that this pathway may have clinical importance as a therapeutic target. 10.1002/cbf.4010 http://creativecommons.org/licenses/by/4.0/