PXD045790

PXD045790 is an original dataset announced via ProteomeXchange.

Title	Microbiome-derived hydroxyphenyl propanoate promotes antitumour immunity by enhancing Gasdermin D cleavage in tumour-associated myeloid cells
Description	The microbiome has a significant impact on immune health and response to immune-stimulating treatments, including cancer immunotherapy. However, the molecular mechanisms by which commensal microbes influence cancer immunology remain poorly understood. Here, we report on the discovery of a class of microbiome-derived metabolites called hydroxyphenyl propanoates (HPP) that enhance tumour immune surveillance in mice and synergize with immune checkpoint blockade (ICB) therapy. HPP molecules act as broad spectrum potentiators of innate immune signalling pathways in tumour-associated myeloid cells by promoting cleavage of the pore-forming protein gasdermin D (GSDMD), a critical effector of canonical and non-canonical inflammasome signalling. Heightened secretion of proinflammatory cytokines from HPP-treated myeloid cells, including IL-1β, promotes NF-κB activity within tumour-infiltrating leukocytes. This leads to heightened anticancer CD8 T cell accumulation, tumour regression, and long-term cancer control by immune checkpoint therapy in mice. Human peripheral blood mononuclear cells (PBMCs) respond to HPP treatment in a similar way. GSDMD cleavage also associates with a favourable response to ICB therapy in advanced stage melanoma patients. Taken together, our study uncovers a mechanism of microbiome-mediated modulation of host antitumour immunity that is modifiable and can be harnessed to enhance the efficacy of cancer immunotherapy. The proteomics part involved searching for hydroxuphenyl pyruvate interactors by using thermal profiling. TMT 10 plex and a method utilizing real-time search was used for quantification.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_12:18:47.019.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045790
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ruzena Filandrova
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-28 13:36:35	ID requested
⏵ 1	2025-05-06 12:18:47	announced

10.6019/PXD045790;

10.1371/journal.ppat.1012766;

Wong HH, Crudgington DRK, Siu L, Sanyal S, Flaviviruses induce ER-specific remodelling of protein synthesis. PLoS Pathog, 20(12):e1012766(2024) [pubmed]

ProteomeXchange project tag: Human Proteome Project

submitter keyword: TMT,Gasdermin D, hydroxuphenyl pyruvate, thermal profiling, THP1-Dual cells

David Schriemer
contact affiliation	University of Calgary
contact email	dschriem@ucalgary.ca
lab head
Ruzena Filandrova
contact affiliation	University of Calgary
contact email	filandrova.ruzena@gmail.com
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/2025/05/PXD045790

PRIDE project URI

• PRIDE
  1. PXD045790
     1. Label: PRIDE project
     2. Name: Microbiome-derived hydroxyphenyl propanoate promotes antitumour immunity by enhancing Gasdermin D cleavage in tumour-associated myeloid cells