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Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma

Overview of attention for article published in Journal for Immunotherapy of Cancer, September 2015
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Title
Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma
Published in
Journal for Immunotherapy of Cancer, September 2015
DOI 10.1186/s40425-015-0081-1
Pubmed ID
Authors

Ahmad A. Tarhini, Haris Zahoor, Yan Lin, Usha Malhotra, Cindy Sander, Lisa H. Butterfield, John M. Kirkwood

Abstract

We evaluated candidate circulating serum cytokines, chemokines and growth factors in patients with locally/regionally advanced melanoma receiving neoadjuvant ipilimumab with toxicity and clinical outcome. Patients were treated with ipilimumab (10 mg/kg IV every 3 weeks, 2 doses) before and after surgery. xMAP multiplex serum testing for 36 functionally selected cytokines and chemokines was performed at baseline and at six weeks (following ipilimumab). Based on our prior data, the association of IL-17 and immune related colitis was tested. Serum cytokines were divided into functional groups (Th1, Th2, Regulatory, Proinflammatory) and were assessed at baseline and week 6 using sparse-group Lasso modeling to assess the association of various cytokine groups with progression free survival (PFS). The linear combination of the cytokines/chemokines in this model was then used as a risk score and a Kaplan-Meier curve was generated to examine the association of the dichotomized score and PFS. Thirty-five patients were enrolled whose staging was: IIIB (3; N2b), IIIC (30; N2c, N3), IV (2). Median follow-up was 18 months. Among 33 evaluable patients, median PFS was 11 months (95 % CI = 6.2-19.2). IL-17 was found to correlate significantly with the incidence of grade 3 diarrhea/colitis when measured at baseline (p = 0.02) with a trend towards significance at 6 weeks (p = 0.06). In the modeling analysis, at baseline, the linear combination of 2 regulatory cytokines [TGF- β1 (ρ = 0.19) and IL-10 (ρ = -0.34)] was significantly associated with PFS (HR 2.66; p = 0.035). No significant correlations with clinical outcomes were found in examining the week 6 cytokines. Baseline IL-17 level was significantly associated with the later development of severe diarrhea/colitis while the combination of baseline TGF- β1 and IL-10 levels were associated with therapeutic clinical outcome after neoadjuvant ipilimumab. These findings warrant further investigation and validation. ClinicalTrials.gov Identifier NCT00972933.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 197 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 197 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 37 19%
Student > Ph. D. Student 21 11%
Student > Bachelor 20 10%
Student > Master 14 7%
Student > Doctoral Student 14 7%
Other 36 18%
Unknown 55 28%
Readers by discipline Count As %
Medicine and Dentistry 72 37%
Immunology and Microbiology 19 10%
Biochemistry, Genetics and Molecular Biology 16 8%
Agricultural and Biological Sciences 9 5%
Pharmacology, Toxicology and Pharmaceutical Science 7 4%
Other 15 8%
Unknown 59 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 18 September 2015.
All research outputs
#14,929,728
of 25,394,764 outputs
Outputs from Journal for Immunotherapy of Cancer
#2,429
of 3,428 outputs
Outputs of similar age
#133,575
of 281,292 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#9
of 13 outputs
Altmetric has tracked 25,394,764 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,428 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.4. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
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 281,292 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.