PXD040266

PXD040266 is an original dataset announced via ProteomeXchange.

Title	Simultaneous targeting of PD-1 and IL2RBY with radiation therapy to inhibit pancreatic cancer growth and metastasis
Description	In patients with pancreatic ductal adenocarcinoma (PDAC), we show that response to radiation therapy (RT) is characterized by increased IL2R and IL2R expression, decreased ILR2 and exhaustion markers. The bispecific PD-1-targeted IL-2 variant (IL2v) immunocytokine with engineered IL-2 cis-targeted to PD-1 and abolished IL2R binding targets the activation of tumor-antigen specific T cells while rescuing them from Treg suppression. Using aPD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival along with profound increase in tumor-infiltrating polyfunctional CD8 T cell subsets with a transcriptionally and metabolically active phenotype, and preferential activation of antigen-specific CD8 T cells. In combination with single dose RT, aPD1-IL2v treatment results in a robust, durable expansion of polyfunctional CD8 T cells, T cell stemness, tumor-specific memory immune response, NK cell activation, and decreased Tregs. These data show that the novel aPD1-IL2v, leads to profound local and distant response in PDAC.
HostingRepository	PRIDE
AnnounceDate	2024-05-24
AnnouncementXML	Submission_2024-05-24_02:32:11.350.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anthony Saviola
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-20 05:00:47	ID requested
⏵ 1	2024-05-24 02:32:12	announced

Piper M, Hoen M, Darragh LB, Knitz MW, Nguyen D, Gadwa J, Durini G, Karakoc I, Grier A, Neupert B, Van Court B, Abdelazeem KNM, Yu J, Olimpo NA, Corbo S, Ross RB, Pham TT, Joshi M, Kedl RM, Saviola AJ, Amann M, Uma, ñ, a P, Codarri Deak L, Klein C, D'Alessandro A, Karam SD, with radiation therapy inhibits pancreatic cancer growth and metastasis. Cancer Cell, 41(5):950-969.e6(2023) [pubmed]

10.1016/j.ccell.2023.04.001;

submitter keyword: timsTOF,pancreatic ductal adenocarcinoma , tumor immunology

Sana D. Karam
contact affiliation	Department of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, United States Department of Microbiology and Immunology, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, United States
contact email	sana.karam@cuanschutz.edu
lab head
Anthony Saviola
contact affiliation	University of Colorado Anschutz Medical Campus
contact email	anthony.saviola@cuanschutz.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/2024/05/PXD040266

PRIDE project URI

• PRIDE
  1. PXD040266
     1. Label: PRIDE project
     2. Name: Simultaneous targeting of PD-1 and IL2RBY with radiation therapy to inhibit pancreatic cancer growth and metastasis