PXD055726

PXD055726 is an original dataset announced via ProteomeXchange.

Title	pathMHC: a workflow to selectively target pathogen-derived MHC peptides in discovery immunopeptidomics experiments for vaccine target identification
Description	Neutrophils have emerged as diverse regulators of tissue states, displaying functions in both the resolution and promotion of tissue inflammation. While neutrophils have widely been associated with tumor promotion, immune suppression, and poor patient outcome, we provide evidence to support direct tumor cytotoxic properties of neutrophils. Using various models of murine breast cancer; we establish that TLR-mediated engagement, combined with complex I inhibition, within the breast tumor microenvironment, acting either directly or indirectly on neutrophils, primes these innate immune cells to acquire direct tumor killing properties, both in vitro and in vivo, and independently of CD8+ T cell immunity. TLR engagement stimulates emergency granulopoiesis, increasing levels of neutrophils in the circulation and infiltrating into tumors without inducing the formation of a pro-metastatic niche. Mechanistically, we show that systemic administration of various TLR agonists, while increasing systemic inflammation, elevates NFB signalling in neutrophils, to contribute to their tumoricidal functions. Moreover, using bulk- and single-cell RNA sequencing, along with proteomics approaches, we show that neutrophils which are trained to acquire these anti-tumorigenic functions both enhance secretory granule production and increase expression NADPH-oxidase machinery. Concomitantly, these tumoricidal neutrophils increase production of toxic levels of reactive oxygen species, which can be overcome with myeloperoxidase inhibitors or overexpression of ROS scavengers. Taken together, we describe a new class of neutrophils that possess direct and intrinsic tumoricidal functions, which can be exploited to eradicate immune cold breast tumors which otherwise are refractory to standard immunotherapies, including immune checkpoint blockade.
HostingRepository	PRIDE
AnnounceDate	2025-07-08
AnnouncementXML	Submission_2025-07-08_15:55:12.986.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD055726
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Owen Leddy
SpeciesList	scientific name: Mycobacterium tuberculosis; NCBI TaxID: 1773; scientific name: Mycobacterium smegmatis; NCBI TaxID: 1772; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-09 01:10:50	ID requested
⏵ 1	2025-07-08 15:55:14	announced

10.6019/PXD055726;

Leddy O, Yuki Y, Carrington M, Bryson BD, White FM, PathMHC: a workflow to selectively target pathogen-derived MHC peptides in discovery immunopeptidomics experiments for vaccine target identification. bioRxiv, ():(2024) [pubmed]

10.1101/2024.09.11.612454;

submitter keyword: bacteria,Mycobacterium tuberculosis,vaccines,tuberculosis,MHC,immunopeptidomics

Forest White
contact affiliation	Massachusetts Institute of Technology
contact email	fwhite@mit.edu
lab head
Owen Leddy
contact affiliation	Massachusetts Institute of Technology
contact email	owenl@mit.edu
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/2025/07/PXD055726

PRIDE project URI

• PRIDE
  1. PXD055726
     1. Label: PRIDE project
     2. Name: pathMHC: a workflow to selectively target pathogen-derived MHC peptides in discovery immunopeptidomics experiments for vaccine target identification