Evidence map›Paper›PMID 30010674›Full record

ArticleNature biotechnology2018

Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme.

Todd A Triplett, Kendra C Garrison, Nicholas Marshall, Moses Donkor, John Blazeck, Candice Lamb, Ahlam Qerqez, Joseph D Dekker, Yuri Tanno, Wei-Cheng Lu and 16 more

Abstract readLetter
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
207citing papers in PubMed, 1 pooled it
7.7field-weighted citation impact, top 2% 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

207 citing papers in PubMed, 1 synthesis or guideline pooled it, 295 citations in OpenAlex.

  1. The immunotherapeutic role of indoleamine 2,3-dioxygenase in head and neck squamous cell carcinoma: A systematic review.Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery · 2021
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  16. Bioresponsive immunomodulator nanocomplex for selective immunoengineering in metastatic lymph nodes.Proceedings of the National Academy of Sciences of the United States of America · 2026
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147 more citing papers are in PubMed but not listed here.

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

26 authors at 6 institutions in 2 countries.

Todd A TriplettDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.
Kendra C GarrisonDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Nicholas MarshallDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Moses DonkorDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
John BlazeckDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Candice LambDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Ahlam QerqezDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Joseph D DekkerDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.ORCID 0000-0002-2068-3529
Yuri TannoDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Wei-Cheng LuDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Christos S KaramitrosDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Kyle FordDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Bing TanDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Xiaoyan M ZhangKyn Therapeutics, Cambridge, Massachusetts, USA.
Karen McGovernKyn Therapeutics, Cambridge, Massachusetts, USA.
Silvia ComaKyn Therapeutics, Cambridge, Massachusetts, USA.
Yoichi KumadaDepartment of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Kyoto, Japan.
Mena S YamanyDepartment of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Enrique SentandreuDepartment of Nutritional Sciences, University of Texas at Austin, Austin, Texas, USA.
George FrommHeat Biologics Inc., Durham, North Carolina, USA.
Stefano TizianiDepartment of Nutritional Sciences, University of Texas at Austin, Austin, Texas, USA.ORCID 0000-0002-7230-0307
Taylor H SchreiberHeat Biologics Inc., Durham, North Carolina, USA.
Mark ManfrediKyn Therapeutics, Cambridge, Massachusetts, USA.
Lauren I R EhrlichDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.ORCID 0000-0002-1697-1755
Everett StoneDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.
George GeorgiouDepartment of Molecular Biosciences, University of Texas at Austin (UT Austin), Austin, Texas, USA.
The University of Texas at Austin · USQ Therapeutics (United States) · USHeat Biologics (United States) · USLivestrong Foundation · USKyoto Institute of Technology · JPMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

Human-Enzyme Mediated, Systemic Depletion of Cystine for Cancer Treatment.R01CA189623 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI DIGIOVANNI, JOHN, GEORGIOU, GEORGE GEORGIOU · 2014 to 2018
$2.9M
NCI NIH HHS R01 CA189623
6 · The paper itself

Abstract

Increased tryptophan (Trp) catabolism in the tumor microenvironment (TME) can mediate immune suppression by upregulation of interferon (IFN)-γ-inducible indoleamine 2,3-dioxygenase (IDO1) and/or ectopic expression of the predominantly liver-restricted enzyme tryptophan 2,3-dioxygenase (TDO). Whether these effects are due to Trp depletion in the TME or mediated by the accumulation of the IDO1 and/or TDO (hereafter referred to as IDO1/TDO) product kynurenine (Kyn) remains controversial. Here we show that administration of a pharmacologically optimized enzyme (PEGylated kynureninase; hereafter referred to as PEG-KYNase) that degrades Kyn into immunologically inert, nontoxic and readily cleared metabolites inhibits tumor growth. Enzyme treatment was associated with a marked increase in the tumor infiltration and proliferation of polyfunctional CD8

Indexed as

Adjuvants, ImmunologicAnimalsCancer VaccinesCell Line, TumorHumansHydrolasesIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineNeoplasmsTumor MicroenvironmentAdjuvants, ImmunologicCancer VaccinesHydrolasesIndoleamine-Pyrrole 2,3,-DioxygenasekynureninaseKynurenine

Identifiers

PMID30010674
PMCPMC6078800
OpenAlexW2883967352

What OpenQuestion holds

Textmetadata
LicenceTDM
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.