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Cancer-Associated Fibroblasts from Lung Tumors Maintain Their Immunosuppressive Abilities after High-Dose Irradiation

Overview of attention for article published in Frontiers in oncology, May 2015
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Title
Cancer-Associated Fibroblasts from Lung Tumors Maintain Their Immunosuppressive Abilities after High-Dose Irradiation
Published in
Frontiers in oncology, May 2015
DOI 10.3389/fonc.2015.00087
Pubmed ID
Authors

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

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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Japan 1 2%
Unknown 45 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 23%
Student > Ph. D. Student 9 19%
Student > Master 8 17%
Student > Doctoral Student 4 9%
Student > Bachelor 3 6%
Other 7 15%
Unknown 5 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 28%
Agricultural and Biological Sciences 8 17%
Medicine and Dentistry 8 17%
Immunology and Microbiology 6 13%
Engineering 2 4%
Other 3 6%
Unknown 7 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 May 2015.
All research outputs
#22,759,802
of 25,374,917 outputs
Outputs from Frontiers in oncology
#15,918
of 22,416 outputs
Outputs of similar age
#239,017
of 279,137 outputs
Outputs of similar age from Frontiers in oncology
#62
of 71 outputs
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So far Altmetric has tracked 22,416 research outputs from this source. They receive a mean Attention Score of 3.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 71 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.