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  Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer

Coscia, F., Lengyel, E., Duraiswamy, J., Ashcroft, B., Bassani-Sternberg, M., Wierer, M., et al. (2018). Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer. Cell, 175(1), 159-170.e16. doi:10.1016/j.cell.2018.08.065.

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 Creators:
Coscia, Fabian1, Author              
Lengyel, Ernst2, Author
Duraiswamy, Jaikumar2, Author
Ashcroft, Bradley2, Author
Bassani-Sternberg, Michal1, Author              
Wierer, Michael1, Author              
Johnson, Alyssa2, Author
Wroblewski, Kristen2, Author
Montag, Anthony2, Author
Yamada, S. Diane2, Author
Lopez-Mendez, Blanca2, Author
Nilsson, Jakob2, Author
Mund, Andreas2, Author
Mann, Matthias1, Author              
Curtis, Marion2, Author
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              

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Free keywords: LONG-TERM SURVIVORS; STRAND BREAK REPAIR; DNA-DAMAGE; COMET ASSAY; REVEALS; ANTIGENS; TUMORS; QUANTIFICATION; METHYLATION; PROGRESSIONBiochemistry & Molecular Biology; Cell Biology;
 Abstract: Most high-grade serous ovarian cancer (HGSOC) patients develop resistance to platinum-based chemotherapy and recur, but 15% remain disease free over a decade. To discover drivers of long-term survival, we quantitatively analyzed the proteomes of platinum-resistant and -sensitive HGSOC patients from minute amounts of formalin-fixed, paraffin-embedded tumors. This revealed cancer/testis antigen 45 (CT45) as an independent prognostic factor associated with a doubling of disease-free survival in advanced-stage HGSOC. Phospho-and interaction proteomics tied CT45 to DNA damage pathways through direct interaction with the PP4 phosphatase complex. In vitro, CT45 regulated PP4 activity, and its high expression led to increased DNA damage and platinum sensitivity. CT45-derived HLA class I peptides, identified by immunopeptidomics, activate patient-derived cytotoxic T cells and promote tumor cell killing. This study highlights the power of clinical cancer proteomics to identify targets for chemo and immunotherapy and illuminate their biological roles.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
 Pages: 28
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 175 (1) Sequence Number: - Start / End Page: 159 - 170.e16 Identifier: ISSN: 0092-8674
CoNE: https://pure.mpg.de/cone/journals/resource/954925463183