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

Research output: Contribution to journal › Journal article › Research › peer-review

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

In: Cell, Vol. 175, No. 1, 2018, p. 159-170.e16.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Coscia, F, Lengyel, E, Duraiswamy, J, Ashcroft, B, Bassani-Sternberg, M, Wierer, M, Johnson, A, Wroblewski, K, Montag, A, Yamada, SD, López-Méndez, B, Nilsson, J, Mund, A, Mann, M & Curtis, M 2018, 'Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer', Cell, vol. 175, no. 1, pp. 159-170.e16. https://doi.org/10.1016/j.cell.2018.08.065

APA

Coscia, F., Lengyel, E., Duraiswamy, J., Ashcroft, B., Bassani-Sternberg, M., Wierer, M., Johnson, A., Wroblewski, K., Montag, A., Yamada, S. D., López-Méndez, B., Nilsson, J., Mund, A., Mann, M., & Curtis, M. (2018). Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer. Cell, 175(1), 159-170.e16. https://doi.org/10.1016/j.cell.2018.08.065

Vancouver

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

Author

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. / Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer. In: Cell. 2018 ; Vol. 175, No. 1. pp. 159-170.e16.

Bibtex

@article{3d51c7eb69cc46979a89bb8b6cb5f7d8,
title = "Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer",
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.",
author = "Fabian Coscia and Ernst Lengyel and Jaikumar Duraiswamy and Bradley Ashcroft and Michal Bassani-Sternberg and Michael Wierer and Alyssa Johnson and Kristen Wroblewski and Anthony Montag and Yamada, {S Diane} and Blanca L{\'o}pez-M{\'e}ndez and Jakob Nilsson and Andreas Mund and Matthias Mann and Marion Curtis",
note = "Copyright {\textcopyright} 2018 Elsevier Inc. All rights reserved.",
year = "2018",
doi = "10.1016/j.cell.2018.08.065",
language = "English",
volume = "175",
pages = "159--170.e16",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and Immunotherapy Target in Ovarian Cancer

AU - Coscia, Fabian

AU - Lengyel, Ernst

AU - Duraiswamy, Jaikumar

AU - Ashcroft, Bradley

AU - Bassani-Sternberg, Michal

AU - Wierer, Michael

AU - Johnson, Alyssa

AU - Wroblewski, Kristen

AU - Montag, Anthony

AU - Yamada, S Diane

AU - López-Méndez, Blanca

AU - Nilsson, Jakob

AU - Mund, Andreas

AU - Mann, Matthias

AU - Curtis, Marion

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2018.08.065

DO - 10.1016/j.cell.2018.08.065

M3 - Journal article

C2 - 30241606

VL - 175

SP - 159-170.e16

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -

ID: 202947227