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

CD39 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 CD...
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Autor*in:	Pedro Briceño [verfasserIn] Elizabeth Rivas-Yañez [verfasserIn] Mariana V. Rosemblatt [verfasserIn] Brian Parra-Tello [verfasserIn] Paula Farías [verfasserIn] Leonardo Vargas [verfasserIn] Valeska Simon [verfasserIn] César Cárdenas [verfasserIn] Alvaro Lladser [verfasserIn] Flavio Salazar-Onfray [verfasserIn] Alvaro A. Elorza [verfasserIn] Mario Rosemblatt [verfasserIn] María Rosa Bono [verfasserIn] Daniela Sauma [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	CD73/NT5E CD8 T cell metabolism cytotoxic antitumor activity

Übergeordnetes Werk:	In: Frontiers in Cell and Developmental Biology - Frontiers Media S.A., 2014, 9(2021)
Übergeordnetes Werk:	volume:9 ; year:2021

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fcell.2021.638037

Katalog-ID:	DOAJ047671580

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allfields	10.3389/fcell.2021.638037 doi (DE-627)DOAJ047671580 (DE-599)DOAJae1c7e0583f64dbba7e19f373c99c234 DE-627 ger DE-627 rakwb eng QH301-705.5 Pedro Briceño verfasserin aut CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CD39 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. CD73/NT5E CD8 T cell metabolism cytotoxic antitumor activity Biology (General) Elizabeth Rivas-Yañez verfasserin aut Elizabeth Rivas-Yañez verfasserin aut Mariana V. Rosemblatt verfasserin aut Mariana V. Rosemblatt verfasserin aut Brian Parra-Tello verfasserin aut Paula Farías verfasserin aut Leonardo Vargas verfasserin aut Valeska Simon verfasserin aut César Cárdenas verfasserin aut Alvaro Lladser verfasserin aut Alvaro Lladser verfasserin aut Flavio Salazar-Onfray verfasserin aut Flavio Salazar-Onfray verfasserin aut Alvaro A. Elorza verfasserin aut Alvaro A. Elorza verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut María Rosa Bono verfasserin aut Daniela Sauma verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.638037 kostenfrei https://doaj.org/article/ae1c7e0583f64dbba7e19f373c99c234 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.638037/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021
spelling	10.3389/fcell.2021.638037 doi (DE-627)DOAJ047671580 (DE-599)DOAJae1c7e0583f64dbba7e19f373c99c234 DE-627 ger DE-627 rakwb eng QH301-705.5 Pedro Briceño verfasserin aut CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CD39 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. CD73/NT5E CD8 T cell metabolism cytotoxic antitumor activity Biology (General) Elizabeth Rivas-Yañez verfasserin aut Elizabeth Rivas-Yañez verfasserin aut Mariana V. Rosemblatt verfasserin aut Mariana V. Rosemblatt verfasserin aut Brian Parra-Tello verfasserin aut Paula Farías verfasserin aut Leonardo Vargas verfasserin aut Valeska Simon verfasserin aut César Cárdenas verfasserin aut Alvaro Lladser verfasserin aut Alvaro Lladser verfasserin aut Flavio Salazar-Onfray verfasserin aut Flavio Salazar-Onfray verfasserin aut Alvaro A. Elorza verfasserin aut Alvaro A. Elorza verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut María Rosa Bono verfasserin aut Daniela Sauma verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.638037 kostenfrei https://doaj.org/article/ae1c7e0583f64dbba7e19f373c99c234 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.638037/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021
allfields_unstemmed	10.3389/fcell.2021.638037 doi (DE-627)DOAJ047671580 (DE-599)DOAJae1c7e0583f64dbba7e19f373c99c234 DE-627 ger DE-627 rakwb eng QH301-705.5 Pedro Briceño verfasserin aut CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CD39 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. CD73/NT5E CD8 T cell metabolism cytotoxic antitumor activity Biology (General) Elizabeth Rivas-Yañez verfasserin aut Elizabeth Rivas-Yañez verfasserin aut Mariana V. Rosemblatt verfasserin aut Mariana V. Rosemblatt verfasserin aut Brian Parra-Tello verfasserin aut Paula Farías verfasserin aut Leonardo Vargas verfasserin aut Valeska Simon verfasserin aut César Cárdenas verfasserin aut Alvaro Lladser verfasserin aut Alvaro Lladser verfasserin aut Flavio Salazar-Onfray verfasserin aut Flavio Salazar-Onfray verfasserin aut Alvaro A. Elorza verfasserin aut Alvaro A. Elorza verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut María Rosa Bono verfasserin aut Daniela Sauma verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.638037 kostenfrei https://doaj.org/article/ae1c7e0583f64dbba7e19f373c99c234 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.638037/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021
allfieldsGer	10.3389/fcell.2021.638037 doi (DE-627)DOAJ047671580 (DE-599)DOAJae1c7e0583f64dbba7e19f373c99c234 DE-627 ger DE-627 rakwb eng QH301-705.5 Pedro Briceño verfasserin aut CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CD39 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. CD73/NT5E CD8 T cell metabolism cytotoxic antitumor activity Biology (General) Elizabeth Rivas-Yañez verfasserin aut Elizabeth Rivas-Yañez verfasserin aut Mariana V. Rosemblatt verfasserin aut Mariana V. Rosemblatt verfasserin aut Brian Parra-Tello verfasserin aut Paula Farías verfasserin aut Leonardo Vargas verfasserin aut Valeska Simon verfasserin aut César Cárdenas verfasserin aut Alvaro Lladser verfasserin aut Alvaro Lladser verfasserin aut Flavio Salazar-Onfray verfasserin aut Flavio Salazar-Onfray verfasserin aut Alvaro A. Elorza verfasserin aut Alvaro A. Elorza verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut María Rosa Bono verfasserin aut Daniela Sauma verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.638037 kostenfrei https://doaj.org/article/ae1c7e0583f64dbba7e19f373c99c234 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.638037/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021
allfieldsSound	10.3389/fcell.2021.638037 doi (DE-627)DOAJ047671580 (DE-599)DOAJae1c7e0583f64dbba7e19f373c99c234 DE-627 ger DE-627 rakwb eng QH301-705.5 Pedro Briceño verfasserin aut CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier CD39 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. CD73/NT5E CD8 T cell metabolism cytotoxic antitumor activity Biology (General) Elizabeth Rivas-Yañez verfasserin aut Elizabeth Rivas-Yañez verfasserin aut Mariana V. Rosemblatt verfasserin aut Mariana V. Rosemblatt verfasserin aut Brian Parra-Tello verfasserin aut Paula Farías verfasserin aut Leonardo Vargas verfasserin aut Valeska Simon verfasserin aut César Cárdenas verfasserin aut Alvaro Lladser verfasserin aut Alvaro Lladser verfasserin aut Flavio Salazar-Onfray verfasserin aut Flavio Salazar-Onfray verfasserin aut Alvaro A. Elorza verfasserin aut Alvaro A. Elorza verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut Mario Rosemblatt verfasserin aut María Rosa Bono verfasserin aut Daniela Sauma verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 9(2021) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:9 year:2021 https://doi.org/10.3389/fcell.2021.638037 kostenfrei https://doaj.org/article/ae1c7e0583f64dbba7e19f373c99c234 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2021.638037/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2021
language	English
source	In Frontiers in Cell and Developmental Biology 9(2021) volume:9 year:2021
sourceStr	In Frontiers in Cell and Developmental Biology 9(2021) volume:9 year:2021
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	CD73/NT5E CD8 T cell metabolism cytotoxic antitumor activity Biology (General)
isfreeaccess_bool	true
container_title	Frontiers in Cell and Developmental Biology
authorswithroles_txt_mv	Pedro Briceño @@aut@@ Elizabeth Rivas-Yañez @@aut@@ Mariana V. Rosemblatt @@aut@@ Brian Parra-Tello @@aut@@ Paula Farías @@aut@@ Leonardo Vargas @@aut@@ Valeska Simon @@aut@@ César Cárdenas @@aut@@ Alvaro Lladser @@aut@@ Flavio Salazar-Onfray @@aut@@ Alvaro A. Elorza @@aut@@ Mario Rosemblatt @@aut@@ María Rosa Bono @@aut@@ Daniela Sauma @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	770398138
id	DOAJ047671580
language_de	englisch
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callnumber-first	Q - Science
author	Pedro Briceño
spellingShingle	Pedro Briceño misc QH301-705.5 misc CD73/NT5E misc CD8 T cell misc metabolism misc cytotoxic misc antitumor activity misc Biology (General) CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity
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topic_title	QH301-705.5 CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity CD73/NT5E CD8 T cell metabolism cytotoxic antitumor activity
topic	misc QH301-705.5 misc CD73/NT5E misc CD8 T cell misc metabolism misc cytotoxic misc antitumor activity misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc CD73/NT5E misc CD8 T cell misc metabolism misc cytotoxic misc antitumor activity misc Biology (General)
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title	CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity
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title_full	CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity
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author_browse	Pedro Briceño Elizabeth Rivas-Yañez Mariana V. Rosemblatt Brian Parra-Tello Paula Farías Leonardo Vargas Valeska Simon César Cárdenas Alvaro Lladser Flavio Salazar-Onfray Alvaro A. Elorza Mario Rosemblatt María Rosa Bono Daniela Sauma
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doi_str_mv	10.3389/fcell.2021.638037
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title_sort	cd73 ectonucleotidase restrains cd8+ t cell metabolic fitness and anti-tumoral activity
callnumber	QH301-705.5
title_auth	CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity
abstract	CD39 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.
abstractGer	CD39 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.
abstract_unstemmed	CD39 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.
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title_short	CD73 Ectonucleotidase Restrains CD8+ T Cell Metabolic Fitness and Anti-tumoral Activity
url	https://doi.org/10.3389/fcell.2021.638037 https://doaj.org/article/ae1c7e0583f64dbba7e19f373c99c234 https://www.frontiersin.org/articles/10.3389/fcell.2021.638037/full https://doaj.org/toc/2296-634X
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author2	Elizabeth Rivas-Yañez Mariana V. Rosemblatt Brian Parra-Tello Paula Farías Leonardo Vargas Valeska Simon César Cárdenas Alvaro Lladser Flavio Salazar-Onfray Alvaro A. Elorza Mario Rosemblatt María Rosa Bono Daniela Sauma
author2Str	Elizabeth Rivas-Yañez Mariana V. Rosemblatt Brian Parra-Tello Paula Farías Leonardo Vargas Valeska Simon César Cárdenas Alvaro Lladser Flavio Salazar-Onfray Alvaro A. Elorza Mario Rosemblatt María Rosa Bono Daniela Sauma
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up_date	2024-07-03T13:25:37.836Z
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