CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity

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dc.contributor.authorBriceño, Pedro
dc.contributor.authorRivas-Yañez, Elizabeth
dc.contributor.authorRosemblatt, Mariana V.
dc.contributor.authorParra-Tello, Brian
dc.contributor.authorFarías, Paula
dc.contributor.authorVargas, Leonardo
dc.contributor.authorSimon, Valeska
dc.contributor.authorCárdenas, César
dc.contributor.authorLladser, Alvaro
dc.contributor.authorSalazar-Onfray, Flavio
dc.contributor.authorElorza, Alvaro A.
dc.contributor.authorRosemblatt, Mario
dc.contributor.authorBono, María Rosa
dc.contributor.authorSauma, Daniela
dc.date.accessioned2023-07-26T21:17:59Z
dc.date.available2023-07-26T21:17:59Z
dc.date.issued2021-02
dc.descriptionIndexación: Scopuses
dc.description.abstractCD39 and CD73 are ectoenzymes that dephosphorylate ATP into its metabolites; ADP, AMP, and adenosine, and thus are considered instrumental in the development of immunosuppressive microenvironments. We have previously shown that within the CD8+ T cell population, naïve and memory cells express the CD73 ectonucleotidase, while terminally differentiated effector cells are devoid of this enzyme. This evidence suggests that adenosine might exert an autocrine effect on CD8+ T cells during T cell differentiation. To study the possible role of CD73 and adenosine during this process, we compared the expression of the adenosinergic signaling components, the phenotype, and the functional properties between CD73-deficient and WT CD8+ T cells. Upon activation, we observed an upregulation of CD73 expression in CD8+ T cells along with an upregulation of the adenosine A2A receptor. Interestingly, when we differentiated CD8+ T cells to Tc1 cells in vitro, we observed that these cells produce adenosine and that CD73-deficient cells present a higher cytotoxic potential evidenced by an increase in IFN-γ, TNF-α, and granzyme B production. Moreover, CD73-deficient cells presented a increased glucose uptake and higher mitochondrial respiration, indicating that this ectonucleotidase restrict the mitochondrial capacity in CD8+ T cells. In agreement, when adoptively transferred, antigen-specific CD73-deficient CD8+ T cells were more effective in reducing the tumor burden in B16.OVA melanoma-bearing mice and presented lower levels of exhaustion markers than wild type cells. All these data suggest an autocrine effect of CD73-mediated adenosine production, limiting differentiation and cytotoxic T cells’ metabolic fitness. © Copyright © 2021 Briceño, Rivas-Yañez, Rosemblatt, Parra-Tello, Farías, Vargas, Simon, Cárdenas, Lladser, Salazar-Onfray, Elorza, Rosemblatt, Bono and Sauma.es
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fcell.2021.638037/full
dc.identifier.citationFrontiers in Cell and Developmental Biology Volume 918 February 2021 Article number 638037es
dc.identifier.doi10.3389/fcell.2021.638037
dc.identifier.issn2296-634X
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/52030
dc.language.isoenes
dc.publisherFrontiers Media S.A.es
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectAntitumor activityes
dc.subjectCD73/NT5Ees
dc.subjectCD8 T celles
dc.subjectCytotoxices
dc.subjectMetabolismes
dc.titleCD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activityes
dc.typeArtículoes
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