Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward
Tumors accumulate metabolites that deactivate infiltrating immune cells and polarize them toward anti-inflammatory phenotypes. We provide a comprehensive review of the complex networks orchestrated by several of the most potent immunosuppressive metabolites, highlighting the impact of adenosine, kyn...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2021-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/10/e003013.full |
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| _version_ | 1823861384792768512 |
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| author | David Munn Maria Rain Jennings John Blazeck |
| author_facet | David Munn Maria Rain Jennings John Blazeck |
| author_sort | David Munn |
| collection | DOAJ |
| description | Tumors accumulate metabolites that deactivate infiltrating immune cells and polarize them toward anti-inflammatory phenotypes. We provide a comprehensive review of the complex networks orchestrated by several of the most potent immunosuppressive metabolites, highlighting the impact of adenosine, kynurenines, prostaglandin E2, and norepinephrine and epinephrine, while discussing completed and ongoing clinical efforts to curtail their impact. Retrospective analyses of clinical data have elucidated that their activity is negatively associated with prognosis in diverse cancer indications, though there is a current paucity of approved therapies that disrupt their synthesis or downstream signaling axes. We hypothesize that prior lukewarm results may be attributed to redundancies in each metabolites’ synthesis or signaling pathway and highlight routes for how therapeutic development and patient stratification might proceed in the future. |
| format | Article |
| id | doaj-art-26073dd770a9408198fc42444cc07e87 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-26073dd770a9408198fc42444cc07e872025-02-09T17:30:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-10-0191010.1136/jitc-2021-003013Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forwardDavid Munn0Maria Rain Jennings1John Blazeck21Augusta University, Augusta, GA, USAChemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USAChemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USATumors accumulate metabolites that deactivate infiltrating immune cells and polarize them toward anti-inflammatory phenotypes. We provide a comprehensive review of the complex networks orchestrated by several of the most potent immunosuppressive metabolites, highlighting the impact of adenosine, kynurenines, prostaglandin E2, and norepinephrine and epinephrine, while discussing completed and ongoing clinical efforts to curtail their impact. Retrospective analyses of clinical data have elucidated that their activity is negatively associated with prognosis in diverse cancer indications, though there is a current paucity of approved therapies that disrupt their synthesis or downstream signaling axes. We hypothesize that prior lukewarm results may be attributed to redundancies in each metabolites’ synthesis or signaling pathway and highlight routes for how therapeutic development and patient stratification might proceed in the future.https://jitc.bmj.com/content/9/10/e003013.full |
| spellingShingle | David Munn Maria Rain Jennings John Blazeck Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward Journal for ImmunoTherapy of Cancer |
| title | Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward |
| title_full | Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward |
| title_fullStr | Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward |
| title_full_unstemmed | Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward |
| title_short | Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward |
| title_sort | immunosuppressive metabolites in tumoral immune evasion redundancies clinical efforts and pathways forward |
| url | https://jitc.bmj.com/content/9/10/e003013.full |
| work_keys_str_mv | AT davidmunn immunosuppressivemetabolitesintumoralimmuneevasionredundanciesclinicaleffortsandpathwaysforward AT mariarainjennings immunosuppressivemetabolitesintumoralimmuneevasionredundanciesclinicaleffortsandpathwaysforward AT johnblazeck immunosuppressivemetabolitesintumoralimmuneevasionredundanciesclinicaleffortsandpathwaysforward |