| Title |
Interferon-γ Drives Treg Fragility to Promote Anti-tumor Immunity
|
|---|---|
| Published in |
Cell, June 2017
|
| DOI | 10.1016/j.cell.2017.05.005 |
| Pubmed ID | |
| Authors |
Abigail E. Overacre-Delgoffe, Maria Chikina, Rebekah E. Dadey, Hiroshi Yano, Erin A. Brunazzi, Gulidanna Shayan, William Horne, Jessica M. Moskovitz, Jay K. Kolls, Cindy Sander, Yongli Shuai, Daniel P. Normolle, John M. Kirkwood, Robert L. Ferris, Greg M. Delgoffe, Tullia C. Bruno, Creg J. Workman, Dario A.A. Vignali |
| Abstract |
Regulatory T cells (Tregs) are a barrier to anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral Treg stability and function but is dispensable for peripheral immune tolerance. Treg-restricted Nrp1 deletion results in profound tumor resistance due to Treg functional fragility. Thus, identifying the basis for Nrp1 dependency and the key drivers of Treg fragility could help to improve immunotherapy for human cancer. We show that a high percentage of intratumoral NRP1(+) Tregs correlates with poor prognosis in melanoma and head and neck squamous cell carcinoma. Using a mouse model of melanoma where Nrp1-deficient (Nrp1(-/-)) and wild-type (Nrp1(+/+)) Tregs can be assessed in a competitive environment, we find that a high proportion of intratumoral Nrp1(-/-) Tregs produce interferon-γ (IFNγ), which drives the fragility of surrounding wild-type Tregs, boosts anti-tumor immunity, and facilitates tumor clearance. We also show that IFNγ-induced Treg fragility is required for response to anti-PD1, suggesting that cancer therapies promoting Treg fragility may be efficacious. |
X Demographics
The data shown below were collected from the profiles of 115 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 35 | 30% |
| United Kingdom | 6 | 5% |
| Spain | 5 | 4% |
| Australia | 3 | 3% |
| France | 2 | 2% |
| Canada | 2 | 2% |
| Denmark | 1 | <1% |
| Brazil | 1 | <1% |
| Peru | 1 | <1% |
| Other | 14 | 12% |
| Unknown | 45 | 39% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 80 | 70% |
| Scientists | 23 | 20% |
| Practitioners (doctors, other healthcare professionals) | 8 | 7% |
| Science communicators (journalists, bloggers, editors) | 4 | 3% |
Mendeley readers
The data shown below were compiled from readership statistics for 560 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | <1% |
| Chile | 1 | <1% |
| Korea, Republic of | 1 | <1% |
| France | 1 | <1% |
| Denmark | 1 | <1% |
| Israel | 1 | <1% |
| Unknown | 553 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 147 | 26% |
| Researcher | 111 | 20% |
| Student > Master | 44 | 8% |
| Student > Bachelor | 37 | 7% |
| Other | 32 | 6% |
| Other | 75 | 13% |
| Unknown | 114 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Immunology and Microbiology | 140 | 25% |
| Biochemistry, Genetics and Molecular Biology | 94 | 17% |
| Medicine and Dentistry | 78 | 14% |
| Agricultural and Biological Sciences | 77 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 10 | 2% |
| Other | 31 | 6% |
| Unknown | 130 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 583. 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 October 2023.
All research outputs
#38,293
of 24,796,076 outputs
Outputs from Cell
#281
of 17,077 outputs
Outputs of similar age
#778
of 321,610 outputs
Outputs of similar age from Cell
#6
of 135 outputs
Altmetric has tracked 24,796,076 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 17,077 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 57.8. This one has done particularly well, scoring higher than 98% of its peers.
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We're also able to compare this research output to 135 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.