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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone
EMBO Reports, Volume 21, No. 6, Article e50162, Year 2020
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Description
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. © 2020 Peter MacCallum Cancer Centre. Published under the terms of the CC BY NC ND 4.0 license
Authors & Co-Authors
Pasam, Anupama
Australia, Melbourne
Peter Maccallum Cancer Centre
Lyons, Ruth J.
Australia, Sydney
Garvan Institute of Medical Research
Ryan, Andrew J.
Unknown Affiliation
Phan, Tri Giang
Australia, Sydney
Unsw Sydney
Australia, Sydney
Garvan Institute of Medical Research
Hayes, Vanessa M.
Australia, Sydney
Unsw Sydney
Australia, Sydney
Garvan Institute of Medical Research
Sandhu, Shahneen K.
Australia, Sydney
The University of Sydney
Corcoran, Niall M.
Australia, Melbourne
Royal Melbourne Hospital
Australia, Melbourne
Peter Maccallum Cancer Centre
Australia, Frankston
Frankston Hospital
Croucher, P. I.
Australia, Sydney
Unsw Sydney
Australia, Sydney
The Kinghorn Cancer Centre
Australia, Sydney
St Vincent's Clinic
Hovens, Christopher M.
Australia, Melbourne
Royal Melbourne Hospital
Statistics
Citations: 51
Authors: 9
Affiliations: 17
Identifiers
Doi:
10.15252/embr.202050162
ISSN:
1469221X
Research Areas
Cancer