مورد إلكتروني
Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone
| العنوان: | Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone |
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| المؤلفون: | Owen, KL, Gearing, LJ, Zanker, DJ, Brockwell, NK, Khoo, WH, Roden, DL, Cmero, M, Mangiola, S, Hong, MK, Spurling, AJ, McDonald, M, Chan, C-L, Pasam, A, Lyons, RJ, Duivenvoorden, HM, Ryan, A, Butler, LM, Mariadason, JM, Phan, TG, Hayes, VM, Sandhu, S, Swarbrick, A, Corcoran, NM, Hertzog, PJ, Croucher, P, Hovens, C, Parker, BS |
| بيانات النشر: | WILEY 2020-04-21 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor-intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor-intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, promoted long-term antitumor immunity, and blocked cancer growth in bone. Key findings were validated in patients, including loss of tumor-intrinsic IFN signaling and immunogenicity in bone metastases compared to primary tumors. Data herein provide a rationale as to why current immunotherapeutics fail in bone-metastatic prostate cancer, and provide a new therapeutic strategy to overcome the inefficacy of immune-based therapies in solid cancers. |
| مصطلحات الفهرس: | Journal Article |
| URL: | |
| الإتاحة: | Open access content. Open access content CC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0 |
| أرقام أخرى: | UMV oai:jupiter.its.unimelb.edu.au:11343/246112 Owen, K. L., Gearing, L. J., Zanker, D. J., Brockwell, N. K., Khoo, W. H., Roden, D. L., Cmero, M., Mangiola, S., Hong, M. K., Spurling, A. J., McDonald, M., Chan, C. -L., Pasam, A., Lyons, R. J., Duivenvoorden, H. M., Ryan, A., Butler, L. M., Mariadason, J. M., Phan, T. G. ,... Parker, B. S. (2020). Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone. EMBO REPORTS, 21 (6), https://doi.org/10.15252/embr.202050162. 10.15252/embr.202050162 1469-3178 1469-221X 1315691516 |
| المصدر المساهم: | UNIV OF MELBOURNE From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1315691516 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |