PXD072994

PXD072994 is an original dataset announced via ProteomeXchange.

Title	Inhibition of KDEL receptors remodels the tumor microenvironment for T cell independent tumor regression
Description	Tumor immunotherapy is supported by low-grade inflammatory conditions at the microenvironment, triggered by immunogenic cell death (ICD). However, ICD is dampened when tumors acquire resistance, affecting immune recognition. KDEL receptors (KDELRs), through a retrograde Golgi-to-ER transport, prevent spontaneous secretion of KDEL proteins. We report that inhibition of a single KDELR in a minor fraction of tumor cells, primarily KDELR2, provokes robust infiltration of macrophages and neutrophils into the tumor microenvironment, resulting in a complete regression of both immunogenic and non-immunogenic tumors independently of T cells. Importantly, in the course of regression, anti-tumor T cells are primed, conferring protection against a second challenge. Recapitulated by intratumoral delivery of siDKELR2 utilizing lipid nanoparticles, we implicate KDELR2 as a target to unleash an unusual robust innate immune response, which represents a tractable approach to initiate an adaptive response downstream, bypassing conventional ICD-inducing therapies. We propose KDELR targeting as a strategy to improve immunotherapy across tumor types, including “cold” tumors resistant to T cell-based immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2026-09-09
AnnouncementXML	Submission_2026-09-09_02:44:02.099.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Belinda Willard
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-13 01:10:16	ID requested
⏵ 1	2026-09-09 02:44:03	announced

Pattanayak SP, Wang H, Willard B, Chan TA, Merrick WC, Lu ZR, Tirosh B, Inhibition of KDEL Receptors Remodels the Tumor Microenvironment for T Cell Independent Tumor Regression. Adv Sci (Weinh), ():e76148(2026) [pubmed]

10.1002/advs.76148;

submitter keyword: KDEL protein, ER stress, tumor microenvironment

Boaz Tirosh
contact affiliation	Department of Biochemistry, School of Medicine, Case Western Reserve University
contact email	bxt213@case.edu
lab head
Belinda Willard
contact affiliation	Cleveland Clinic
contact email	willarb@ccf.org
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/2026/09/PXD072994

PRIDE project URI

• PRIDE
  1. PXD072994
     1. Label: PRIDE project
     2. Name: Inhibition of KDEL receptors remodels the tumor microenvironment for T cell independent tumor regression