Title |
Suppression of Metastases Using a New Lymphocyte Checkpoint Target for Cancer Immunotherapy
|
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Published in |
Cancer Discovery, April 2016
|
DOI | 10.1158/2159-8290.cd-15-0944 |
Pubmed ID | |
Authors |
Stephen J. Blake, Kimberley Stannard, Jing Liu, Stacey Allen, Michelle C.R. Yong, Deepak Mittal, Amelia Roman Aguilera, John J. Miles, Viviana P. Lutzky, Lucas Ferrari de Andrade, Ludovic Martinet, Marco Colonna, Kazuyoshi Takeda, Florian Kühnel, Engin Gurlevik, Günter Bernhardt, Michele W.L. Teng, Mark J. Smyth |
Abstract |
CD96 has recently been shown as a negative regulator of mouse NK cell activity, with Cd96-/- mice displaying hyper-responsive NK cells upon immune challenge. In this study we have demonstrated that blocking CD96 with a monoclonal antibody inhibited experimental metastases in three different tumor models. The anti-metastatic activity of anti-CD96 was dependent on NK cells, CD226 (DNAM-1) and IFN-γ, but independent of activating Fc receptors. Anti-CD96 was more effective in combination with anti-CTLA4, anti-PD1 or doxorubicin chemotherapy. Blocking CD96 in Tigit-/- mice significantly reduced experimental and spontaneous metastases compared to its activity in WT mice. Co-blockade of CD96 and PD1 potently inhibited lung metastases, with the combination increasing local NK cell IFN-γ production and infiltration. Overall these data demonstrate that blocking CD96 is a new and complementary immunotherapeutic strategy to reduce tumor metastases. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 14% |
Unknown | 6 | 86% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 7 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Australia | 2 | <1% |
France | 2 | <1% |
United States | 1 | <1% |
Germany | 1 | <1% |
Unknown | 222 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 48 | 21% |
Student > Ph. D. Student | 43 | 19% |
Student > Master | 21 | 9% |
Other | 18 | 8% |
Student > Bachelor | 17 | 7% |
Other | 35 | 15% |
Unknown | 46 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 52 | 23% |
Biochemistry, Genetics and Molecular Biology | 44 | 19% |
Medicine and Dentistry | 32 | 14% |
Agricultural and Biological Sciences | 26 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 7 | 3% |
Other | 16 | 7% |
Unknown | 51 | 22% |