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Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients

Overview of attention for article published in Journal of Translational Medicine, April 2017
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Title
Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients
Published in
Journal of Translational Medicine, April 2017
DOI 10.1186/s12967-017-1182-z
Pubmed ID
Authors

A. Schiza, J. Wenthe, S. Mangsbo, E. Eriksson, Anders Nilsson, T. H. Tötterman, A. Loskog, G. Ullenhag

Abstract

Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide. Cells were analyzed by flow cytometry while plasma samples were analyzed by a multi-array proteomics. All patients had an increased Teffector/Tregulatory cell ratio post therapy. Simultaneously, the death receptors TNFR1 and TRAIL-R2 were significantly up-regulated post treatment. Stem cell factor (SCF), E-selectin, and CD6 correlated to enhanced overall survival while a high level of granulocytic myeloid-derived suppressor cells (gMDSCs), IL8, IL10, TGFb1, CCL4, PlGF and Fl3t ligand was highest in patients with short survival. AdCD40L intratumoral injection induced desirable systemic immune effects that correlated to prolonged survival. Further studies using CD40 stimulation in malignant melanoma are warranted. Trial registration The 002:CD40L trial "Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors" (clinicalTrials.gov identifier: NCT01455259) was registered at September 2011.

X Demographics

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 44 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 16%
Student > Ph. D. Student 6 14%
Researcher 4 9%
Student > Master 4 9%
Student > Doctoral Student 3 7%
Other 7 16%
Unknown 13 30%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 23%
Medicine and Dentistry 6 14%
Immunology and Microbiology 4 9%
Agricultural and Biological Sciences 2 5%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Other 5 11%
Unknown 15 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 29 April 2017.
All research outputs
#13,548,595
of 22,965,074 outputs
Outputs from Journal of Translational Medicine
#1,596
of 4,013 outputs
Outputs of similar age
#158,486
of 310,204 outputs
Outputs of similar age from Journal of Translational Medicine
#30
of 70 outputs
Altmetric has tracked 22,965,074 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,013 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one has gotten more attention than average, scoring higher than 57% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 310,204 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 70 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.