Mesenchymal stromal cells derived from cervical cancer produce high amounts of adenosine to suppress cytotoxic T lymphocyte functions

宫颈癌间充质基质细胞产生大量腺苷来抑制细胞毒性T淋巴细胞功能

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作者:María de Lourdes Mora-García, Rosario García-Rocha, Omar Morales-Ramírez, Juan José Montesinos, Benny Weiss-Steider, Jorge Hernández-Montes, Luis Roberto Ávila-Ibarra, Christian Azucena Don-López, Marco Antonio Velasco-Velázquez, Vianey Gutiérrez-Serrano, Alberto Monroy-García

Background

In recent years, immunomodulatory mechanisms of mesenchymal stem/stromal cells (MSCs) from bone marrow and other "classic" sources have been described. However, the phenotypic and functional properties of tumor MSCs are poorly understood. The

Conclusions

This study suggests that CeCa-MSCs play an important role in the suppression of the anti-tumor immune response in CeCa through the purinergic pathway.

Methods

We determined the expression and functional activity of the membrane-associated ectonucleotidases CD39 and CD73 on CeCa-MSCs and normal cervical tissue-derived MSCs (NCx-MSCs). We also analyzed their immunosuppressive capacity to decrease proliferation, activation and effector cytotoxic T (CD8+) lymphocyte function through the generation of adenosine (Ado).

Results

We detected that CeCa-MSCs express higher levels of CD39 and CD73 ectonucleotidases in cell membranes compared to NCx-MSCs, and that this feature was associated with the ability to strongly suppress the proliferation, activation and effector functions of cytotoxic T-cells through the generation of large amounts of Ado from the hydrolysis of ATP, ADP and AMP nucleotides. Conclusions: This study suggests that CeCa-MSCs play an important role in the suppression of the anti-tumor immune response in CeCa through the purinergic pathway.

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