ATP and cancer immunosurveillance
While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor microenvironment (TME), extracellular ATP operates as a potent signal transducer. The net effects of purinergic signaling on the biology of the...
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| Veröffentlicht in: | The EMBO journal 2021-07, Vol.40 (13), p.e108130-n/a |
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| creator | Kepp, Oliver Bezu, Lucillia Yamazaki, Takahiro Di Virgilio, Francesco Smyth, Mark J Kroemer, Guido Galluzzi, Lorenzo |
| description | While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor microenvironment (TME), extracellular ATP operates as a potent signal transducer. The net effects of purinergic signaling on the biology of the TME depend not only on the specific receptors and cell types involved, but also on the activation status of
cis
‐ and
trans
‐regulatory circuitries. As an additional layer of complexity, extracellular ATP is rapidly catabolized by ectonucleotidases, culminating in the accumulation of metabolites that mediate distinct biological effects. Here, we discuss the molecular and cellular mechanisms through which ATP and its degradation products influence cancer immunosurveillance, with a focus on therapeutically targetable circuitries.
Graphical Abstract
This review summarizes our current view on the dual roles of signaling via adenosine triphosphate and its degradation products in the tumor microenvironment, affecting intracellular metabolism as well as crosstalk between malignant and immune cells. |
| doi_str_mv | 10.15252/embj.2021108130 |
| format | Article |
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cis
‐ and
trans
‐regulatory circuitries. As an additional layer of complexity, extracellular ATP is rapidly catabolized by ectonucleotidases, culminating in the accumulation of metabolites that mediate distinct biological effects. Here, we discuss the molecular and cellular mechanisms through which ATP and its degradation products influence cancer immunosurveillance, with a focus on therapeutically targetable circuitries.
Graphical Abstract
This review summarizes our current view on the dual roles of signaling via adenosine triphosphate and its degradation products in the tumor microenvironment, affecting intracellular metabolism as well as crosstalk between malignant and immune cells.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.15252/embj.2021108130</identifier><identifier>PMID: 34121201</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adenosine triphosphate ; ADORA2A ; ATP ; autophagy ; Bioenergetics ; Biological effects ; Cancer ; CD39 ; CD73 ; Cell death ; Degradation products ; EMBO03 ; EMBO19 ; EMBO21 ; immune checkpoint inhibitors ; immunogenic cell death ; Immunosurveillance ; Metabolites ; Review ; Reviews ; Tumor microenvironment</subject><ispartof>The EMBO journal, 2021-07, Vol.40 (13), p.e108130-n/a</ispartof><rights>The Author(s) 2021</rights><rights>2021 The Authors</rights><rights>2021 EMBO</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4960-f688ab16a72535034ba1210b2d295998aa1ec4a90315eacdbc21e1e003c900fa3</citedby><cites>FETCH-LOGICAL-c4960-f688ab16a72535034ba1210b2d295998aa1ec4a90315eacdbc21e1e003c900fa3</cites><orcidid>0000-0002-6081-9558 ; 0000-0002-9334-4405 ; 0000-0003-3566-1362 ; 0000-0003-2257-8500</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246257/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246257/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27903,27904,41099,42168,45553,45554,46387,46811,51554,53769,53771</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.15252/embj.2021108130$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc></links><search><creatorcontrib>Kepp, Oliver</creatorcontrib><creatorcontrib>Bezu, Lucillia</creatorcontrib><creatorcontrib>Yamazaki, Takahiro</creatorcontrib><creatorcontrib>Di Virgilio, Francesco</creatorcontrib><creatorcontrib>Smyth, Mark J</creatorcontrib><creatorcontrib>Kroemer, Guido</creatorcontrib><creatorcontrib>Galluzzi, Lorenzo</creatorcontrib><title>ATP and cancer immunosurveillance</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><description>While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor microenvironment (TME), extracellular ATP operates as a potent signal transducer. The net effects of purinergic signaling on the biology of the TME depend not only on the specific receptors and cell types involved, but also on the activation status of
cis
‐ and
trans
‐regulatory circuitries. As an additional layer of complexity, extracellular ATP is rapidly catabolized by ectonucleotidases, culminating in the accumulation of metabolites that mediate distinct biological effects. Here, we discuss the molecular and cellular mechanisms through which ATP and its degradation products influence cancer immunosurveillance, with a focus on therapeutically targetable circuitries.
Graphical Abstract
This review summarizes our current view on the dual roles of signaling via adenosine triphosphate and its degradation products in the tumor microenvironment, affecting intracellular metabolism as well as crosstalk between malignant and immune cells.</description><subject>Adenosine triphosphate</subject><subject>ADORA2A</subject><subject>ATP</subject><subject>autophagy</subject><subject>Bioenergetics</subject><subject>Biological effects</subject><subject>Cancer</subject><subject>CD39</subject><subject>CD73</subject><subject>Cell death</subject><subject>Degradation products</subject><subject>EMBO03</subject><subject>EMBO19</subject><subject>EMBO21</subject><subject>immune checkpoint inhibitors</subject><subject>immunogenic cell death</subject><subject>Immunosurveillance</subject><subject>Metabolites</subject><subject>Review</subject><subject>Reviews</subject><subject>Tumor microenvironment</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkM1PAjEQxRujEUTvHjFevIAzs-1uNzEmSPArGD3guemWgkv2A1sWw3_vIkSDifHUZPp77808xk4RuihI0KXNk1mXgBBBYgB7rIk8hA5BJPZZEyjEDkcZN9iR9zMAEDLCQ9YIOBISYJOd9UYvbV2M20YXxrp2mudVUfrKLW2aZevZMTuY6Mzbk-3bYq-3g1H_vjN8vnvo94Ydw-M6chJKqRMMdUQiEBDwRNcZkNCYYhHHUmu0husYAhRWm3FiCC1agMDEABMdtNj1xndeJbkdG1ssnM7U3KW5ditV6lTt_hTpm5qWSyWJhySi2uBia-DK98r6hcpTb-z6CltWXpHgEJGMAqrR81_orKxcUZ-3pkIZIoe4pmBDGVd67-zkexkE9dW_WvevfvqvJVcbyUea2dW_vBo83TzuyHEj97WymFr3s9efkZ9hgZaz</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Kepp, Oliver</creator><creator>Bezu, Lucillia</creator><creator>Yamazaki, Takahiro</creator><creator>Di Virgilio, Francesco</creator><creator>Smyth, Mark J</creator><creator>Kroemer, Guido</creator><creator>Galluzzi, Lorenzo</creator><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>John Wiley and Sons Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6081-9558</orcidid><orcidid>https://orcid.org/0000-0002-9334-4405</orcidid><orcidid>https://orcid.org/0000-0003-3566-1362</orcidid><orcidid>https://orcid.org/0000-0003-2257-8500</orcidid></search><sort><creationdate>20210701</creationdate><title>ATP and cancer immunosurveillance</title><author>Kepp, Oliver ; 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The net effects of purinergic signaling on the biology of the TME depend not only on the specific receptors and cell types involved, but also on the activation status of
cis
‐ and
trans
‐regulatory circuitries. As an additional layer of complexity, extracellular ATP is rapidly catabolized by ectonucleotidases, culminating in the accumulation of metabolites that mediate distinct biological effects. Here, we discuss the molecular and cellular mechanisms through which ATP and its degradation products influence cancer immunosurveillance, with a focus on therapeutically targetable circuitries.
Graphical Abstract
This review summarizes our current view on the dual roles of signaling via adenosine triphosphate and its degradation products in the tumor microenvironment, affecting intracellular metabolism as well as crosstalk between malignant and immune cells.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34121201</pmid><doi>10.15252/embj.2021108130</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-6081-9558</orcidid><orcidid>https://orcid.org/0000-0002-9334-4405</orcidid><orcidid>https://orcid.org/0000-0003-3566-1362</orcidid><orcidid>https://orcid.org/0000-0003-2257-8500</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature OA Free Journals |
| subjects | Adenosine triphosphate ADORA2A ATP autophagy Bioenergetics Biological effects Cancer CD39 CD73 Cell death Degradation products EMBO03 EMBO19 EMBO21 immune checkpoint inhibitors immunogenic cell death Immunosurveillance Metabolites Review Reviews Tumor microenvironment |
| title | ATP and cancer immunosurveillance |
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