PXD027167

PXD027167 is an original dataset announced via ProteomeXchange.

Title	Metabolic modulation of tumors with engineered bacteria for immunotherapy
Description	The availability of L-arginine in tumors is a key determinant of an efficient anti-tumor T cell response. Consequently, elevation of typically low L-arginine levels within the tumor may greatly potentiate the anti-tumor responses of immune checkpoint inhibitors, such as PD-L1 blocking antibodies. However, currently no means are available to locally increase intra-tumoral L-arginine levels. Here, we used a synthetic biology approach to develop an engineered probiotic Escherichia coli Nissle 1917 strain that colonizes tumors and continuously converts ammonia, a metabolic waste product that accumulates in tumors, into L-arginine. Colonization of tumors with these bacteria elevated intra-tumoral L-arginine concentrations, increased the amount of tumor-infiltrating T cells, and had striking synergistic effects with PD-L1 blocking antibodies in the clearance of tumors. The anti-tumor effect of the living therapeutic was mediated by L-arginine and was dependent on T cells. These results show that engineered microbial therapies enable metabolic modulation of the tumor microenvironment leading to enhanced efficacy of immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2021-07-13
AnnouncementXML	Submission_2021-10-13_00:09:28.427.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matteo Pecoraro
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-07 09:24:37	ID requested
1	2021-07-13 02:05:22	announced
⏵ 2	2021-10-13 00:09:29	announced	2021-10-13: Updated publication reference for PubMed record(s): 34616044.

Canale FP, Basso C, Antonini G, Perotti M, Li N, Sokolovska A, Neumann J, James MJ, Geiger S, Jin W, Theurillat JP, West KA, Leventhal DS, Lora JM, Sallusto F, Geiger R, Metabolic modulation of tumours with engineered bacteria for immunotherapy. Nature, 598(7882):662-666(2021) [pubmed]

submitter keyword: Cancer Immunotherapy, Metabolic modulation of tumors, L-arginine, Synthetic biology, Bacteria-based therapies

Roger Geiger
contact affiliation	Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland. Institute of Oncology Research, Università della Svizzera italiana, Bellinzona, Switzerland.
contact email	roger.geiger@irb.usi.ch
lab head
Matteo Pecoraro
contact affiliation	Institute for Research in Biomedicine, Via Vincenzo Vela 6 - CH-6500 Bellinzona
contact email	matteo.pecoraro@irb.usi.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/2021/07/PXD027167

PRIDE project URI

• PRIDE
  1. PXD027167
     1. Label: PRIDE project
     2. Name: Metabolic modulation of tumors with engineered bacteria for immunotherapy