PXD042428-2

PXD042428 is an original dataset announced via ProteomeXchange.

Title	Macrophage regulation by the Pentose Phosphate Pathway in the TME
Description	Macrophages in the B-cell lymphoma microenvironment represent a functional node in progression and therapeutic response. We assessed metabolic regulation of macrophages in the context of therapeutic antibody mediated phagocytosis. Pentose phosphate pathway (PPP) inhibition by specific inhibitors and genetic targeting induced increased phagocytic lymphoma cell clearance. Moreover, macrophages provided decreased support for survival of lymphoma cells. PPP inhibition induced metabolic activation, cytoskeletal re-modelling and pro-inflammatory polarization of macrophages. A connection between PPP and immune regulation was identified as mechanism of macrophage repolarization. PPP inhibition causes suppression of glycogen synthesis and subsequent modulation of the immune modulatory STAT1-IRG1-itaconate axis. PPP inhibition rewired macrophage activation in vivo. Addition of the PPP inhibitor S3 to antibody therapy achieved significant increased overall survival in an aggressive B cell lymphoma mouse model. We hypothesize the PPP as key regulator and targetable modulator of macrophage activity in lymphoma to improve efficacy of immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2024-11-27
AnnouncementXML	Submission_2024-11-27_02:56:07.095.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Theresa Bock
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-23 05:21:17	ID requested
1	2024-11-25 03:44:16	announced
⏵ 2	2024-11-27 02:56:07	announced	2024-11-27: Updated project metadata.

10.1016/J.XCRM.2024.101830;

submitter keyword: B-cell lymphoma, Pentose phosphate pathway,Macrophage

Christian Pallasch
contact affiliation	1 Department I of Internal Medicine, Center for Integrated Oncology (CIO) Köln-Bonn. 2 Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD)
contact email	christian.pallasch@uk-koeln.de
lab head
Theresa Bock
contact affiliation	CECAD Research Center, University of Cologne
contact email	tbock2@uni-koeln.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042428
     1. Label: PRIDE project
     2. Name: Macrophage regulation by the Pentose Phosphate Pathway in the TME