Evidence map›Paper›PMID 26029659›Full record

ArticleFrontiers in oncology2015

Cancer-associated fibroblasts from lung tumors maintain their immunosuppressive abilities after high-dose irradiation.

Laia Gorchs, Turid Hellevik, Jack-Ansgar Bruun, Ketil-Andre Camilio, Samer Al-Saad, Tor-Brynjar Stuge, Inigo Martinez-Zubiaurre

Open access · goldAbstract read
In one paragraph

Article in Frontiers in oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

49 citing papers in PubMed, 70 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

7 authors at 2 institutions in 1 country.

Laia GorchsDepartment of Clinical Medicine, University of Tromsø , Tromsø , Norway.
Turid HellevikDepartment of Oncology and Radiotherapy, University Hospital of Northen Norway , Tromsø , Norway.
Jack-Ansgar BruunDepartment of Medical Biology, University of Tromsø , Tromsø , Norway.
Ketil-Andre CamilioDepartment of Medical Biology, University of Tromsø , Tromsø , Norway.
Samer Al-SaadDepartment of Medical Biology, University of Tromsø , Tromsø , Norway ; Department of Pathology, University Hospital of Northern Norway , Tromsø , Norway.
Tor-Brynjar StugeDepartment of Medical Biology, University of Tromsø , Tromsø , Norway.
Inigo Martinez-ZubiaurreDepartment of Clinical Medicine, University of Tromsø , Tromsø , Norway.
UiT The Arctic University of Norway · NOUniversity Hospital of North Norway · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulating evidence supports the notion that high-dose (>5 Gy) radiotherapy (RT) regimens are triggering stronger pro-immunogenic effects than standard low-dose (2 Gy) regimens. However, the effects of RT on certain immunoregulatory elements in tumors remain unexplored. In this study, we have investigated the effects of high-dose radiotherapy (HD-RT) on the immunomodulating functions of cancer-associated fibroblasts (CAFs). Primary CAF cultures were established from lung cancer specimens derived from patients diagnosed for non-small cell lung cancer. Irradiated and non-irradiated CAFs were examined for immunomodulation in experiments with peripheral blood mononuclear cells from random, healthy donors. Regulation of lymphocytes behavior was checked by lymphocyte proliferation assays, lymphocyte migration assays, and T-cell cytokine production. Additionally, CAF-secreted immunoregulatory factors were studied by multiplex protein arrays, ELISAs, and by LC-MS/MS proteomics. In all functional assays, we observed a powerful immunosuppressive effect exerted by CAF-conditioned medium on activated T-cells (p > 0.001), and this effect was sustained after a single radiation dose of 18 Gy. Relevant immunosuppressive molecules such as prostaglandin E2, interleukin-6, and -10, or transforming growth factor-β were found in CAF-conditioned medium, but their secretion was unchanged after irradiation. Finally, immunogenic cell death responses in CAFs were studied by exploring the release of high motility group box-1 and ATP. Both alarmins remained undetectable before and after irradiation. In conclusion, CAFs play a powerful immunosuppressive effect over activated T-cells, and this effect remains unchanged after HD-RT. Importantly, CAFs do not switch on immunogenic cell death responses after exposure to HD-RT.

Indexed as

cancer-associated fibroblastshigh-dose radiationimmunogenic cell deathlung cancertumor immunology

Identifiers

PMID26029659
PMCPMC4429237
OpenAlexW1529178741

What OpenQuestion holds

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Registered trials

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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.