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Long term impact of CTLA4 blockade immunotherapy on regulatory and effector immune responses in patients with melanoma

Overview of attention for article published in Journal of Translational Medicine, July 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (74th percentile)

Mentioned by

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12 tweeters

Citations

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18 Dimensions

Readers on

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39 Mendeley
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Title
Long term impact of CTLA4 blockade immunotherapy on regulatory and effector immune responses in patients with melanoma
Published in
Journal of Translational Medicine, July 2018
DOI 10.1186/s12967-018-1563-y
Pubmed ID
Authors

Janet Retseck, Alexis Nasr, Yan Lin, Huang Lin, Prateek Mendiratta, Lisa H. Butterfield, Ahmad A. Tarhini

Abstract

We previously reported early on-treatment significant modulation in circulating regulatory T cell (Treg), myeloid derived suppressor cells (MDSC) and antigen-specific type I CD4+ and CD8+ T cells that correlated with clinical outcome in regionally advanced melanoma patients treated with neoadjuvant ipilimumab. Here, we investigated the long term immunologic impact of CTLA4 blockade. Patients were treated with ipilimumab given at 10 mg/kg IV every 3 weeks for 2 doses bracketing surgery. Blood specimens were collected at baseline and during treatment for up to 9 months. We tested immune responses at 3, 6, and 9 months utilizing multicolor flow cytometry. We compared frequencies of circulating Treg and MDSC on-study to baseline levels, as well as frequencies of CD4+ and CD8+ T cells specific to shared tumor-associated antigens (Gp-100, MART-1, NY-ESO-1). Levels of Treg significantly increased when measured at 6 weeks following ipilimumab but returned to baseline by 3 months, with no significant difference in Treg levels between relapsed and relapse-free groups at 3, 6 or 9 months. However, lower baseline levels of circulating Treg (CD4+CD25hi+CD39+) were significantly associated with better relapse free survival (RFS) (p = 0.04). Levels of circulating monocytic HLA-DR+/loCD14+ MDSC were lower at baseline in the relapse-free group and further decreased at 6 weeks, though the differences did not reach statistical significance including measurements at 3, 6 or 9 months. We detected evidence of type I (interferon-γ producing), activated (CD69+) CD4+ and CD8+ antigen-specific T cell immunity against cancer-testis (NY-ESO-1) as well as melanocytic lineage (MART-1, gp100) antigens in the absence of therapeutic vaccination. These responses were significantly boosted at 6 weeks and persisted at 3, 6 and 9 months following the initiation of ipilimumab. Lower Treg levels at baseline are significantly associated with RFS and increased Treg frequency after CTLA4 blockade was only transient. Lower MDSC was also associated with RFS and MDSC levels were further decreased after ipilimumab. Tumor specific effector immune responses are boosted with CTLA4 blockade and tend to be durable. Trial registration ClinicalTrials.gov Identifier: NCT00972933.

Twitter Demographics

The data shown below were collected from the profiles of 12 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Other 5 13%
Student > Ph. D. Student 5 13%
Student > Postgraduate 4 10%
Student > Bachelor 3 8%
Student > Doctoral Student 3 8%
Other 6 15%
Unknown 13 33%
Readers by discipline Count As %
Immunology and Microbiology 8 21%
Biochemistry, Genetics and Molecular Biology 7 18%
Medicine and Dentistry 7 18%
Veterinary Science and Veterinary Medicine 1 3%
Materials Science 1 3%
Other 0 0%
Unknown 15 38%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 12 August 2018.
All research outputs
#3,326,913
of 18,659,856 outputs
Outputs from Journal of Translational Medicine
#509
of 3,336 outputs
Outputs of similar age
#71,748
of 287,255 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 1 outputs
Altmetric has tracked 18,659,856 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,336 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.3. This one has done well, scoring higher than 84% 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 287,255 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 74% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them