Evidence map›Paper›PMID 33109232›Full record

ArticleBreast cancer research : BCR2020

Differential kynurenine pathway metabolism in highly metastatic aggressive breast cancer subtypes: beyond IDO1-induced immunosuppression.

Benjamin Heng, Ayse A Bilgin, David B Lovejoy, Vanessa X Tan, Heloisa H Milioli, Laurence Gluch, Sonia Bustamante, Tharani Sabaretnam, Pablo Moscato, Chai K Lim and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

37 citing papers in PubMed, 56 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Benjamin HengDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. benjamin.heng@mq.edu.au.
Ayse A BilginFaculty of Sciences and Engineering, Macquarie University, Sydney, Australia.
David B LovejoyDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Vanessa X TanDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Heloisa H MilioliSchool of Environmental and Life Sciences, The University of Newcastle, Callaghan, Australia.
Laurence GluchThe Strathfield Breast Centre, Strathfield, Australia.
Sonia BustamanteBioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia.
Tharani SabaretnamDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Pablo MoscatoSchool of Electrical Engineering and Life Sciences, The University of Newcastle, Callaghan, Australia.
Chai K LimDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Gilles J GuilleminDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. gilles.guillemin@mq.edu.au.ORCID 0000-0001-8105-4470
Macquarie University · AUUniversity of Newcastle Australia · AUUNSW Sydney · AU

Funding

ARC Discovery Project DP120102576Australian Research Council (ARC) Future Fellowship FT12010060Cancer Institute NSW 13/DATA/1-03
6 · The paper itself

Abstract

backgroundImmunotherapy has recently been proposed as a promising treatment to stop breast cancer (BrCa) progression and metastasis. However, there has been limited success in the treatment of BrCa with immune checkpoint inhibitors. This implies that BrCa tumors have other mechanisms to escape immune surveillance. While the kynurenine pathway (KP) is known to be a key player mediating tumor immune evasion and while there are several studies on the roles of the KP in cancer, little is known about KP involvement in BrCa.

methodsTo understand how KP is regulated in BrCa, we examined the KP profile in BrCa cell lines and clinical samples (n = 1997) that represent major subtypes of BrCa (luminal, HER2-enriched, and triple-negative (TN)). We carried out qPCR, western blot/immunohistochemistry, and ultra-high pressure liquid chromatography on these samples to quantify the KP enzyme gene, protein, and activity, respectively.

resultsWe revealed that the KP is highly dysregulated in the HER2-enriched and TN BrCa subtype. Gene, protein expression, and KP metabolomic profiling have shown that the downstream KP enzymes KMO and KYNU are highly upregulated in the HER2-enriched and TN BrCa subtypes, leading to increased production of the potent immunosuppressive metabolites anthranilic acid (AA) and 3-hydroxylanthranilic acid (3HAA).

conclusionsOur findings suggest that KMO and KYNU inhibitors may represent new promising therapeutic targets for BrCa. We also showed that KP metabolite profiling can be used as an accurate biomarker for BrCa subtyping, as we successfully discriminated TN BrCa from other BrCa subtypes.

Indexed as

Metabolic Networks and PathwaysTumor EscapeAdultAgedBiomarkers, TumorBreast NeoplasmsCase-Control StudiesCell Line, TumorCohort StudiesDatabases, GeneticFemaleGene Expression Regulation, NeoplasticHumansHydrolasesIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineBiomarkers, TumorHydrolasesIDO1 protein, humanIndoleamine-Pyrrole 2,3,-DioxygenasekynureninaseKynurenineKynurenine 3-MonooxygenaseBiomarkerBreast cancerImmune evasionKynurenine pathwayTryptophan

Identifiers

PMID33109232
PMCPMC7590459
OpenAlexW3096231745

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.