|  Help  |  About  |  Contact Us

Publication : PARP-inhibition reprograms macrophages toward an anti-tumor phenotype.

First Author  Wang L Year  2022
Journal  Cell Rep Volume  41
Issue  2 Pages  111462
PubMed ID  36223740 Mgi Jnum  J:360364
Mgi Id  MGI:7366844 Doi  DOI:10.1016/j.celrep.2022.111462
Citation  Wang L, et al. (2022) PARP-inhibition reprograms macrophages toward an anti-tumor phenotype. Cell Rep 41(2):111462
abstractText  Poly(ADP)ribosylation inhibitors (PARPis) are toxic to cancer cells with homologous recombination (HR) deficiency but not to HR-proficient cells in the tumor microenvironment (TME), including tumor-associated macrophages (TAMs). As TAMs can promote or inhibit tumor growth, we set out to examine the effects of PARP inhibition on TAMs in BRCA1-related breast cancer (BC). The PARPi olaparib causes reprogramming of TAMs toward higher cytotoxicity and phagocytosis. A PARPi-related surge in NAD+ increases glycolysis, blunts oxidative phosphorylation, and induces reverse mitochondrial electron transport (RET) with an increase in reactive oxygen species (ROS) and transcriptional reprogramming. This reprogramming occurs in the absence or presence of PARP1 or PARP2 and is partially recapitulated by addition of NAD derivative methyl-nicotinamide (MNA). In vivo and ex vivo, the effect of olaparib on TAMs contributes to the anti-tumor efficacy of the PARPi. In vivo blockade of the "don't-eat-me signal" with CD47 antibodies in combination with olaparib improves outcomes in a BRCA1-related BC model.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

13 Bio Entities

Trail: Publication

0 Expression