PXD039789

PXD039789 is an original dataset announced via ProteomeXchange.

Title	Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming
Description	Immune evasion is an important hallmark of cancer ensured by diverse strategies, including immunosuppression and downregulation of antigen presentation. Here, to restore immunogenicity of cancer cells, we employed the minimal gene regulatory network of highly immunogenic type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen presenting cells (APCs). We showed that enforced expression of PU.1, IRF8 and BATF3 (PIB) was sufficient to induce cDC1 phenotype in 33 cell lines derived from human and mouse hematological and solid tumors. PIB gradually modified the cancer cell transcriptional and epigenetic program imposing global antigen presentation and cDC1 gene signatures within 9 days. cDC1 reprogramming restored the expression of antigen presentation complexes as well as co-stimulatory molecules at the cell surface, leading to the presentation of endogenous antigens on MHC-I, and to CD8+ T cell mediated killing. Functionally, tumor- APCs acquired the ability to uptake and process exogenous proteins and dead cells, secreted inflammatory cytokines and cross-presented antigens to naïve CD8+ T cells. Importantly, tumor-APCs were efficiently generated at the single cell level from primary cancer cells of 7 solid tumors that presented antigens to memory and naïve T-cells, as well as to activated patient-specific intra-tumoral lymphocytes. Alongside antigen presentation, tumor-APCs harboring TP53, KRAS and PTEN mutations showed impaired tumorigenicity in vitro and in vivo. Finally, using in vivo mouse models of melanoma, we showed that intra-tumoral injection of tumor-APCs promoted lymphoid infiltration, delayed tumor growth and increased survival. The anti-tumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors enabling tumor eradication. Our approach combines cDC1’s antigen processing and presenting abilities with endogenous generation of tumor antigens and serves as a platform for the development of novel immunotherapies based on endowed antigen presentation in cancer cells.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:08:32.789.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michal Bassani-Sternberg
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-01 08:03:06	ID requested
1	2023-10-24 12:02:46	announced
⏵ 2	2023-11-14 09:08:42	announced	2023-11-14: Updated project metadata.

Zimmermannova O, Ferreira AG, Ascic E, Velasco Santiago M, Kurochkin I, Hansen M, Met Ö, Caiado I, Shapiro IE, Michaux J, Humbert M, Soto-Cabrera D, Benonisson H, Silv, é, rio-Alves R, Gomez-Jimenez D, Bernardo C, Bauden M, Andersson R, H, ö, glund M, Miharada K, Nakamura Y, Hugues S, Greiff L, Lindstedt M, Rosa FF, Pires CF, Bassani-Sternberg M, Svane IM, Pereira CF, Restoring tumor immunogenicity with dendritic cell reprogramming. Sci Immunol, 8(85):eadd4817(2023) [pubmed]

submitter keyword: cancer antigens,Cell reprogramming, immunopeptidomics, antigen presentation

Michal Bassani-Sternberg
contact affiliation	Ludwig Institute for Cancer Research Department of Oncology, University hospital of Lausanne, Switzerland
contact email	Michal.bassani@chuv.ch
lab head
Michal Bassani-Sternberg
contact affiliation	UNIL/CHUV
contact email	michal.bassani@chuv.ch
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/2023/10/PXD039789

PRIDE project URI

• PRIDE
  1. PXD039789
     1. Label: PRIDE project
     2. Name: Restoring Tumor Immunogenicity with Dendritic Cell Reprogramming