Evidence map›Paper›PMID 35133062›Full record

ArticleCancer science2022

Impacts of the STING-IFNAR1-STAT1-IRF1 pathway on the cellular immune reaction induced by fractionated irradiation.

Junyan Du, Shun-Ichiro Kageyama, Riu Yamashita, Hidenari Hirata, Yumi Hakozaki, Masayuki Okumura, Atsushi Motegi, Hidehiro Hojo, Masaki Nakamura, Yasuhiro Hirano and 9 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
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  3. Inhibition of RAB7 promotes CD8American journal of cancer research · 2026
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  11. PARP7-mediated ADP-ribosylation of FRA1 promotes cancer cell growth by repressing IRF1- and IRF3-dependent apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Review
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  14. Review
  15. Article
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

19 authors at 4 institutions in 2 countries.

Junyan DuDivision of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.ORCID https://orcid.org/0000-0003-1440-5538
Shun-Ichiro KageyamaDivision of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.
Riu YamashitaDivision of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
Hidenari HirataDivision of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.
Yumi HakozakiDepartment of Radiation Oncology, National Cancer Center Hospital East, Chiba, Japan.
Masayuki OkumuraDivision of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.
Atsushi MotegiDivision of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.
Hidehiro HojoDivision of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.
Masaki NakamuraDivision of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.
Yasuhiro HiranoDivision of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.
Hironori SunakawaDepartment of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan.
Tatsunori MinamideDepartment of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan.
Daisuke KotaniDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
Kosuke TanakaDivision of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
Tomonori YanoDepartment of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan.
Takashi KojimaDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.ORCID https://orcid.org/0000-0002-2554-8334
Akihiro OhashiDivision of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
Katsuya TsuchiharaDivision of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.ORCID https://orcid.org/0000-0001-7507-2349
Tetsuo AkimotoDivision of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Chiba, Japan.
National Cancer Center Hospital East · JPTranslational Research in Oncology · FRUbe Frontier University · JPChiba Cancer Center · JP

Funding

Grants-in-Aid for Scientific Research KAKENHI 18K07740National Cancer Center Research and Development Fund 21-A-8National Cancer Center Research and Development Fund 31-A-10
6 · The paper itself

Abstract

Radiotherapy (RT) combined with immune checkpoint inhibitors has recently produced outstanding results and is expected to be adaptable for various cancers. However, the precise molecular mechanism by which immune reactions are induced by fractionated RT is still controversial. We aimed to investigate the mechanism of the immune response regarding multifractionated, long-term radiation, which is most often combined with immunotherapy. Two human esophageal cancer cell lines, KYSE-450 and OE-21, were irradiated by fractionated irradiation (FIR) daily at a dose of 3 Gy in 5 d/wk for 2 weeks. Western blot analysis and RNA sequencing identified type I interferon (IFN) and the stimulator of IFN genes (STING) pathway as candidates that regulate immune response by FIR. We inhibited STING, IFNAR1, STAT1, and IFN regulatory factor 1 (IRF1) and investigated the effects on the immune response in cancer cells and the invasion of surrounding immune cells. We herein revealed type I IFN-dependent immune reactions and the positive feedback of STING, IRF1, and phosphorylated STAT1 induced by FIR. Knocking out STING, IFNAR1, STAT1, and IRF1 resulted in a poorer immunological response than that in WT cells. The STING-KO KYSE-450 cell line showed significantly less invasion of PBMCs than the WT cell line under FIR. In the analysis of STING-KO cells and migrated PBMCs, we confirmed the occurrence of STING-dependent immune activation under FIR. In conclusion, we identified that the STING-IFNAR1-STAT1-IRF1 axis regulates immune reactions in cancer cells triggered by FIR and that the STING pathway also contributes to immune cell invasion of cancer cells.

Indexed as

Esophageal NeoplasmsImmunityInterferon Regulatory Factor-1STAT1 Transcription FactorCell LineHumansInterferon Type IMembrane ProteinsReceptor, Interferon alpha-betaSTING ProteinIFNAR1 protein, humanInterferon Regulatory Factor-1Interferon Type IIRF1 protein, humanMembrane ProteinsReceptor, Interferon alpha-betaSTAT1 protein, humanSTAT1 Transcription FactorSTING1 protein, humanSTING ProteincGAS-STINGesophageal cancerfractionated irradiationimmune checkpointimmune response

Identifiers

PMID35133062
PMCPMC8990811
OpenAlexW4210857128

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.