Immunosuppressive metabolites in tumoral immune evasion: Redundancies, clinical efforts, and pathways forward

Maria Rain Jennings, David Munn, John Blazeck

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Article numbere003013
JournalJournal for ImmunoTherapy of Cancer
Issue number10
StatePublished - Oct 19 2021


  • adenosine
  • immunotherapy
  • indoleamine-pyrrole 2,3-dioxygenase
  • metabolic networks and pathways
  • tumor escape

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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