PR002161 (Project)

Id Namespace:

UCSD Metabolomics Workbench

Identifier Namespace (Entity type)

Dcc Asset:

MW submission packet 20250922.zip

Processed File (Entity type)

Dcc:

Metabolomics

DCC (Entity type)

Persistent Id:http://dx.doi.org/10.21228/M89258

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 induced increased phagocytic lymphoma cell clearance by macrophages in vitro, in primary human Chronic lymphocytic leukemia (CLL) patient co-cultures, and in mouse models. Addition of the PPP inhibitor S3 to antibody therapy achieved significantly prolonged overall survival in an aggressive B-cell lymphoma mouse model. PPP inhibition induced metabolic activation and pro-inflammatory polarization of macrophages while it decreased macrophages´ support for survival of lymphoma cells empowering anti-lymphoma function. As mechanism of macrophage repolarization, the link between PPP and immune regulation was identified. PPP inhibition causes decreased glycogen level and subsequent modulation of the immune modulatory UDPG-Stat1-Irg1-Itaconate axis. Thus, we hypothesize the PPP as key regulator and targetable modulator of macrophage activity in lymphoma to improve efficacy of immunotherapies and prolong survival.

Results found

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	Label	Description
	PPR00001 Project (Entity type)	Metabolomics
	SU003645 Subject (Entity type)	A subject from Metabolomics produced as part of the PR002161 project
	SA386408 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002161 project
	SA386404 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002161 project
	SA386388 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002161 project
	SA386393 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002161 project
	SA386401 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002161 project
	SA386423 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002161 project
	SA386410 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002161 project
	SA386418 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002161 project