Fatty acid transport protein 2 reprograms neutrophils in cancer
| العنوان: | Fatty acid transport protein 2 reprograms neutrophils in cancer |
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| المؤلفون: | Brian Nam, Zach Schug, Fang Wang, Vladimir A. Tyurin, Maureen E. Murphy, Alessandra De Leo, Maria Blasi, Paul N. Black, Cindy Lin, Subhasree Basu, Michael J. Guarino, Valerian E. Kagan, Charles Mulligan, Robert H. Vonderheide, Yulia Nefedova, Dmitry I. Gabrilovich, Paul M. Lieberman, Filippo Veglia, Laxminarasimha Donthireddy, Concetta C. DiRusso, Gregory A. Masters, Tsun Ki Jerrick To, Andrew V. Kossenkov, Emanuela Ricciotti, Neil Hockstein |
| المصدر: | Nature. 569:73-78 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Multidisciplinary, biology, Chemistry, Cancer, medicine.disease, 3. Good health, Transport protein, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Immune system, Downregulation and upregulation, 030220 oncology & carcinogenesis, medicine, biology.protein, Cancer research, Arachidonic acid, Prostaglandin E2, Transcription factor, STAT5, medicine.drug |
| الوصف: | Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are pathologically activated neutrophils that are crucial for the regulation of immune responses in cancer. These cells contribute to the failure of cancer therapies and are associated with poor clinical outcomes. Despite recent advances in the understanding of PMN-MDSC biology, the mechanisms responsible for the pathological activation of neutrophils are not well defined, and this limits the selective targeting of these cells. Here we report that mouse and human PMN-MDSCs exclusively upregulate fatty acid transport protein 2 (FATP2). Overexpression of FATP2 in PMN-MDSCs was controlled by granulocyte-macrophage colony-stimulating factor, through the activation of the STAT5 transcription factor. Deletion of FATP2 abrogated the suppressive activity of PMN-MDSCs. The main mechanism of FATP2-mediated suppressive activity involved the uptake of arachidonic acid and the synthesis of prostaglandin E2. The selective pharmacological inhibition of FATP2 abrogated the activity of PMN-MDSCs and substantially delayed tumour progression. In combination with checkpoint inhibitors, FATP2 inhibition blocked tumour progression in mice. Thus, FATP2 mediates the acquisition of immunosuppressive activity by PMN-MDSCs and represents a target to inhibit the functions of PMN-MDSCs selectively and to improve the efficiency of cancer therapy. |
| تدمد: | 1476-4687 0028-0836 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::aec0236c86fb05724c4f73ad5736e6b2 https://doi.org/10.1038/s41586-019-1118-2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........aec0236c86fb05724c4f73ad5736e6b2 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14764687 00280836 |
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