Evidence map›Paper›PMID 34667078›Full record

ReviewJournal for immunotherapy of cancer2021

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

Maria Rain Jennings, David Munn, John Blazeck

Open access · goldAbstract readReview
In one paragraph

Review in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 53 citations in OpenAlex.

  1. Trial
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  6. IK-175, an Oral Aryl Hydrocarbon Receptor Inhibitor, Alone and with Nivolumab in Patients with Advanced Solid Tumors and Urothelial Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
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  14. Integrating Metabolic Modulation and Nanomedicine for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Maria Rain JenningsChemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.ORCID 0000-0002-2898-5222
David MunnMedical College of Georgia, Augusta University, Augusta, Georgia, USA.
John BlazeckChemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA john.blazeck@chbe.gatech.edu.ORCID 0000-0002-6110-2938
Georgia Institute of Technology · USAugusta University · US

Funding

Project 3: Targeting Bax signaling to overcome treatment resistance in NSCLCP50CA217691 · NCI · EMORY UNIVERSITY · PI DENG, XINGMING · 2019 to 2024
$10.1M
Reprogramming the TME for immunogenic antigen-presentationR01CA103320 · NCI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MUNN, DAVID H. · 2003 to 2024
$6.0M
PTEN, Tregs and MDSCs in the tumor microenvironmentR01CA211229 · NCI · AUGUSTA UNIVERSITY · PI MUNN, DAVID H. · 2017 to 2021
$1.7M
NCI NIH HHS P50 CA217691NCI NIH HHS R01 CA103320NCI NIH HHS R01 CA211229
6 · The paper itself

Abstract

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.

Indexed as

HumansImmune EvasionImmunosuppression TherapyImmunotherapyNeoplasmsadenosineimmunotherapyindoleamine-pyrrole 2,3-dioxygenasemetabolic networks and pathwaystumor escape

Identifiers

PMID34667078
PMCPMC8527165
OpenAlexW3206510554

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.