Details

Autor(en) / Beteiligte

• Coscia, Fabian
• Lengyel, Ernst
• Duraiswamy, Jaikumar
• Ashcroft, Bradley
• Bassani-Sternberg, Michal
• Wierer, Michael
• Johnson, Alyssa
• Wroblewski, Kristen
• Montag, Anthony
• Yamada, S. Diane
• López-Méndez, Blanca
• Nilsson, Jakob
• Mund, Andreas
• Mann, Matthias
• Curtis, Marion

Titel

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

Ist Teil von

• Cell, 2018-09, Vol.175 (1), p.159-170.e16

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •Clinical proteomics workflow for the analysis of archived tumor samples•Cancer/testis antigen 45 enhances chemosensitivity in metastatic ovarian cancer•CT45 is a novel protein phosphatase 4 regulator linked to DNA damage signaling•CT45 derived peptides bind HLA-I receptors and activate cytotoxic T cells Integrative proteomic analysis in clinical tumor samples identifies a platinum sensitivity regulator and immunotherapy target for ovarian cancer and illustrates the clinical potential of cancer proteomics.