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PXD040266

PXD040266 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSimultaneous targeting of PD-1 and IL2RBY with radiation therapy to inhibit pancreatic cancer growth and metastasis
DescriptionIn 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.
HostingRepositoryPRIDE
AnnounceDate2024-05-24
AnnouncementXMLSubmission_2024-05-24_02:32:11.350.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAnthony Saviola
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-20 05:00:47ID requested
12024-05-24 02:32:12announced
Publication List
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;
Keyword List
submitter keyword: timsTOF,pancreatic ductal adenocarcinoma , tumor immunology
Contact List
Sana D. Karam
contact affiliationDepartment 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 emailsana.karam@cuanschutz.edu
lab head
Anthony Saviola
contact affiliationUniversity of Colorado Anschutz Medical Campus
contact emailanthony.saviola@cuanschutz.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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