Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone
Details
Publication Year 2020-06-04, Volume 21, Issue #6, Page e50162
Journal Title
EMBO Reports
Abstract
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.
Publisher
Embo Press
Keywords
*bone metastasis; *dormancy; *immune evasion; *prostate cancer; *type I interferon;
WEHI Research Division(s)
Bioinformatics
Open Access at Publisher's Site
https://doi.org/10.15252/embr.202050162
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-03-04 09:47:04
Last Modified: 2021-03-08 11:21:00
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