Title |
Interferon-γ Drives Treg Fragility to Promote Anti-tumor Immunity
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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
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
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% |