PXD020871-1

PXD020871 is an original dataset announced via ProteomeXchange.

Title	Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer
Description	Standard cancer therapy targets tumor cells without considering the possible collateral damage on the tumor microenvironment that could impair therapy response. Employing patient-derived tumor organoids and primary stroma cells or a novel murine rectal cancer model, we show that interleukin-1 (IL-1 dependent inflammatory cancer-associated fibroblast (iCAF) polarization triggers oxidative DNA damage in iCAFs leading to p53-mediated therapy-induced senescence associated with changes in matrisome composition, chemoradiotherapy resistance and disease progression. IL-1 inhibition, prevention of iCAF senescence or senolytic therapy sensitizes mice to irradiation. In rectal cancer patients a dominant iCAF gene signature as well as lower IL-1 receptor antagonist (IL-1RA) serum levels correlate with poor prognosis. Moreover, conditioned supernatant from patient tumor organoids renders fibroblasts susceptible to radiation-induced senescence in an IL-1-dependent manner. Collectively, we unravel a critical role for iCAFs in therapy resistance and identify IL-1 signaling as an attractive target for stroma-repolarization and prevention of CAF senescence.
HostingRepository	PRIDE
AnnounceDate	2022-02-08
AnnouncementXML	Submission_2022-02-08_02:48:08.380.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adele Nicolas
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated lysine; monoacetylated residue; monohydroxylated residue; 2-pyrrolidone-5-carboxylic acid (Pro); monohydroxylated proline; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-12 06:42:51	ID requested
⏵ 1	2022-02-08 02:48:08	announced
2	2023-11-14 08:53:45	announced	2023-11-14: Updated project metadata.

10.1016/J.CCELL.2022.01.004;

submitter keyword: rectal cancer, chemoradiotherapy, extracellular matrix, matrisome, TMT labeling

Florian R. Greten
contact affiliation	Institute for Tumor Biology and Experimental Therapy Georg-Speyer-Haus 60596 Frankfurt/Main Germany
contact email	greten@gsh.uni-frankfurt.de
lab head
Adele Nicolas
contact affiliation	Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt/Main, Germany Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt/Main, Germany
contact email	nicolas@gsh.uni-frankfurt.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD020871

PRIDE project URI

• PRIDE
  1. PXD020871
     1. Label: PRIDE project
     2. Name: Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer