Adenosine augments the production of IL-10 in cervical cancer cells through interaction with the A2B adenosine receptor, resulting in protection against the activity of cytotoxic T cells. (June 2020)

• Record Type: Journal Article
• 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
• Is Part Of: Cytokine. Volume 130(2020)
• Publication Date: 2020-06
• Subjects: Cervical cancer -- Interleukin-10 -- HLA Class I downregulation -- Adenosinergic pathway -- A2B adenosine receptor -- Immune evasion; Ado adenosine -- Anti-IL-10 anti-human neutralizing antibody against IL-10 -- APCP adenosine 5′-(α, β-methylene)diphosphate -- ARs adenosine receptors -- ATCC American Type Culture Collection -- CD39 ectonucleoside triphosphate diphosphohydrolase-1 -- CD73 5′-ectonucleotidase -- CeCa Cervical cancer -- CTLs cytotoxic T lymphocytes -- HIF-1α Hypoxia-inducible factor 1α -- HLA-I major histocompatibility complex class I molecules -- HR-HPV high-risk human papillomavirus -- Ino inosine -- MDSCs myeloid-derived suppressor cells -- MFI mean fluorescence intensity -- MRS1754 8-[4-[((4-cyanophenyl)carbamoylmethyl)oxy]phenyl]-1, 3-di(n-propyl)xanthine hydrate -- NECA 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-b-D-ribofuranuronamide -- NK natural killer cells -- rhIL-10 recombinant human interleukin-10 -- SILs low-grade squamous intraepithelial lesions -- TME tumor microenvironment -- T regs regulatory T cells -- ZM241385 4-(-2-[7-amino-2-{2-furyl}{1, 2, 4}triazolo{2, 3-α} {1, 3, 5}triazin-5-yl-amino]ethyl)phenol; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155082
• Languages: English
• ISSNs: 1043-4666

Abstract

Graphical abstract: Highlights: Adenosine increases the expression and production of IL-10 in cervical cancer cells. Adenosine favors the evasion of immune recognition in cervical/uterine cancer cells. A2B R blockade in cervical cancer cells favors CTL-mediated immune recognition. Abstract: 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 A2B 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.