Evidence map›Paper›PMID 33410234›Full record

ArticleCancer science2021

Tryptophan 2,3-dioxygenase in tumor cells is associated with resistance to immunotherapy in renal cell carcinoma.

Makoto Sumitomo, Kiyoshi Takahara, Kenji Zennami, Tomomi Nagakawa, Yasuhiro Maeda, Kazuya Shiogama, Yasuko Yamamoto, Yoshinari Muto, Takuhisa Nukaya, Masashi Takenaka and 5 more

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

Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 15% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
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  7. Kynurenine Pathway after Kidney Transplantation: Friend or Foe?International journal of molecular sciences · 2024
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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

15 authors at 1 institution in 1 country.

Makoto SumitomoFujita Cancer Center, Fujita Health University, Toyoake, Japan.ORCID https://orcid.org/0000-0003-2589-922X
Kiyoshi TakaharaDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Kenji ZennamiFujita Cancer Center, Fujita Health University, Toyoake, Japan.ORCID https://orcid.org/0000-0001-8455-7364
Tomomi NagakawaDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Yasuhiro MaedaResearch Promotion and Support Headquarters, Center for Joint Research Facilities Support, Fujita Health University, Toyoake, Japan.
Kazuya ShiogamaDepartment of Pathology, School of Health Sciences, Fujita Health University, Toyoake, Japan.
Yasuko YamamotoDepartment of Disease Control and Prevention, Fujita Health University, Toyoake, Japan.ORCID https://orcid.org/0000-0001-8825-9188
Yoshinari MutoDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Takuhisa NukayaDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Masashi TakenakaDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Kosuke FukayaDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Manabu IchinoDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Hitomi SasakiDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Kuniaki SaitoDepartment of Disease Control and Prevention, Fujita Health University, Toyoake, Japan.
Ryoichi ShirokiDepartment of Urology, School of Medicine, Fujita Health University, Toyoake, Japan.
Fujita Health University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme associated with immunomodulation through its regulation of the tryptophan-kynurenine (Kyn) pathway in advanced cancers, including metastatic renal cell carcinoma (mRCC). However, the failure of IDO1 inhibitors when used in combination with immune checkpoint inhibitors (ICIs), as observed in clinical trials, raises a number of questions. This study aimed to investigate the association of tryptophan 2,3-dioxygenase (TDO) and IDO1 with cancer development and resistance to immunotherapy in patients with RCC. In our analysis of RCC tissue samples, tissue Kyn levels were elevated in advanced-stage RCC and correlated well with TDO expression levels in RCC tumor cells. In patients with mRCC, TDO rather than IDO1 was expressed in RCC tumor cells, showing a strong association with Kyn expression. Furthermore, immunohistochemical staining of TDO was strongly associated with the staining intensity of forkhead box P3, as well as ICI therapy response and survival in patients with mRCC. Our study is the first to show that TDO expression in tumor tissues is associated with progression and survival, confirming its potential as a predictive biomarker of primary resistance to immunotherapy in patients with mRCC. Our findings suggest that strategies aimed at inhibiting TDO, rather than IDO1, in combination with ICI therapy may aid in the control of mRCC progression.

Indexed as

AgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Renal CellCell Line, TumorChemotherapy, AdjuvantDisease ProgressionDrug Resistance, NeoplasmFemaleHumansImmune Checkpoint InhibitorsImmunohistochemistryIndoleamine-Pyrrole 2,3,-DioxygenaseKidneyKidney NeoplasmsKynurenineIDO1 protein, humanImmune Checkpoint InhibitorsIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineTryptophanTryptophan OxygenasebiomarkerIDO1immune checkpoint inhibitorrenal cell carcinomaTDO

Identifiers

PMID33410234
PMCPMC7935775
OpenAlexW3118481597

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.