دورية أكاديمية
Reactive Neutrophil Responses Dependent on the Receptor Tyrosine Kinase c-MET Limit Cancer Immunotherapy
| العنوان: | Reactive Neutrophil Responses Dependent on the Receptor Tyrosine Kinase c-MET Limit Cancer Immunotherapy |
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| المؤلفون: | Glodde, Nicole, Bald, Tobias, van den Boorn-Konijnenberg, Debby, Nakamura, Kyohei, O'Donnell, Jake S., Szczepanski, Sabrina, Brandes, Maria, Eickhoff, Sarah, Das, Indrajit, Shridhar, Naveen, Hinze, Daniel, Rogava, Meri, van der Sluis, Tetje C., Ruotsalainen, Janne J., Gaffal, Evelyn, Landsberg, Jennifer, Ludwig, Kerstin U., Wilhelm, Christoph, Riek-Burchardt, Monika, Müller, Andreas J., Gebhardt, Christoffer, Scolyer, Richard A., Long, Georgina V., Janzen, Viktor, Teng, Michele W. L., Kastenmüller, Wolfgang, Mazzone, Massimiliano, Smyth, Mark J., Tüting, Thomas, Hölzel, Michael |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2017 |
| المجموعة: | The University of Queensland: UQ eSpace |
| مصطلحات موضوعية: | HGF, T cells, bone marrow, c-MET, cancer immunotherapy, lymph node, melanoma, neutrophils, plasticity, therapy resistance, 2403 Immunology, 2723 Immunology and Allergy, 2725 Infectious Diseases |
| الوصف: | Inhibitors of the receptor tyrosine kinase c-MET are currently used in the clinic to target oncogenic signaling in tumor cells. We found that concomitant c-MET inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in murine cancer models by increasing effector T cell infiltration in tumors. This therapeutic effect was independent of tumor cell-intrinsic c-MET dependence. Mechanistically, c-MET inhibition impaired the reactive mobilization and recruitment of neutrophils into tumors and draining lymph nodes in response to cytotoxic immunotherapies. In the absence of c-MET inhibition, neutrophils recruited to T cell-inflamed microenvironments rapidly acquired immunosuppressive properties, restraining T cell expansion and effector functions. In cancer patients, high serum levels of the c-MET ligand HGF correlated with increasing neutrophil counts and poor responses to checkpoint blockade therapies. Our findings reveal a role for the HGF/c-MET pathway in neutrophil recruitment and function and suggest that c-MET inhibitor co-treatment may improve responses to cancer immunotherapy in settings beyond c-MET-dependent tumors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1097-4180 1074-7613 |
| العلاقة: | orcid:0000-0001-7098-7240; 217/674-1 FUGG; ALT945-2015; 1124690; 1944/3-1; GE 2152/2-1; TU 90/8-1; SFB704; SFB854; HO4281/2-1; 308459; 1078671; 1098960; Not set; MU 3742/2-1; EXC 1023; EKFS 2013_A297 |
| الإتاحة: | https://doi.org/10.1016/j.immuni.2017.09.012Test https://espace.library.uq.edu.au/view/UQ:690677Test |
| رقم الانضمام: | edsbas.4102D1BA |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10974180 10747613 |
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