PXD070607-1

PXD070607 is an original dataset announced via ProteomeXchange.

Title	Lymphodepleting chemotherapy potentiates neoantigen-directed T-cell therapy by enhancing antigen presentation
Description	Adoptive cell therapy (ACT) targeting tumor-specific antigens holds promise for solid-tumors, but limited neoantigen presentation remains a key barrier to efficacy. Here, we identify and characterize a T-cell receptor (TCR), T104, for the KRAS.G12V mutation, a prevalent neoantigen in colorectal, lung, and pancreatic cancers. TCR-T104 selectively recognize and kill KRAS.G12V expressing tumor cells. Combining T-cell therapy with lymphodepleting chemotherapy significantly enhance tumor-cell killing, particularly by TCR-T-cells, tumor-infiltrating lymphocytes (TILs) and T-cell engager antibodies across multiple cancer types and target antigens. Mechanistically, chemotherapy upregulates immunoproteasome activity and HLA-I surface expression. HLA-Immunopeptidome analyses reveal that chemotherapy remodels the antigenic landscape across tumor cell-lines and In vivo models, increasing peptide abundance and hydrophobicity, while altering proteasomal cleavage preferences. These findings establish a synergistic role for chemotherapy in enhancing neoantigen presentation and T-cell-mediated tumor recognition and suggest that fine-tuning these regimens could improve ACT efficacy, particularly in tumors with low-abundance neoantigens. **Proteomics data have been deposited to the PRIDE (ProteomeXchange) repository under accession number PXD061178. This dataset expands on data previously deposited under accession PXD061178.Contains proteomic data of SW620 A03 as well HLA-1 Immunopeptidomic MIapaca2 cell line treated with Chemo and SW620 A03 tumors harvested from NSG mice treat with chemothetapy.**
HostingRepository	PRIDE
AnnounceDate	2026-01-12
AnnouncementXML	Submission_2026-01-11_18:04:00.508.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shira Sagie
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-11 16:02:55	ID requested
⏵ 1	2026-01-11 18:04:01	announced

10.1016/j.xcrm.2025.102506;

submitter keyword: KRAS G12V,lymphodepleting chemotherapy,proteomics, KRAS G12C, TCR therapy, neoantigens, colon cancer.,Adoptive cell therapy,immunotheraphy, pancreatic cancer

Yardena Samuels
contact affiliation	Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
contact email	yardena.samuels@weizmann.ac.il
lab head
Shira Sagie
contact affiliation	The Weizmann Institute of Science
contact email	shira.sagie-groher@weizmann.ac.il
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/2026/01/PXD070607

PRIDE project URI

• PRIDE
  1. PXD070607
     1. Label: PRIDE project
     2. Name: Lymphodepleting chemotherapy potentiates neoantigen-directed T-cell therapy by enhancing antigen presentation