Adenosine augments the production of IL-10 in cervical cancer cells through interaction with the A 2B adenosine receptor, resulting in protection against the activity of cytotoxic T cells

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2020-04, Vol.130, p.155082
• Main Authors: Torres-Pineda, Daniela Berenice, Mora-García, María de Lourdes, García-Rocha, Rosario, Hernández-Montes, Jorge, Weiss-Steider, Benny, Montesinos-Montesinos, Juan José, Don-López, Christian Azucena, Marín-Aquino, Luis Antonio, Muñóz-Godínez, Ricardo, Ibarra, Luis Roberto Ávila, López Romero, Ricardo, Monroy-García, Alberto
• Format: Article
• Language: English
• ISSN: 1096-0023

Cervical cancer (CeCa) produces large amounts of IL-10, which downregulates the major histocompatibility complex class I molecules (HLA-I) in cancer cells and inhibits the immune response mediated by cytotoxic T lymphocytes (CTLs). In this study, we analyzed the ability of CeCa cells to produce IL-10 through the CD73-adenosine pathway and its effect on the downregulation of HLA-I molecules to evade CTL-mediated immune recognition. CeCa cells cultured in the presence of ≥10 µM AMP or adenosine produced 4.5-6 times as much IL-10 as unstimulated cells. The silencing of CD73 or the blocking of A R with the specific antagonist MRS1754 reversed this effect. In addition, IL-10 decreased the expression of HLA-I molecules, resulting in the protection of CeCa cells against the cytotoxic activity of CTLs. The addition of MRS1754 or anti-IL-10 reversed the decrease in HLA-I molecules and favored the cytotoxic activity of CTLs. These results strongly suggest the presence of a feedback loop encompassing the adenosinergic pathway, the production of IL-10, and the downregulation of HLA-I molecules in CeCa cells that favors immune evasion and thus tumor progression. This pathway may have clinical importance as a therapeutic target.