PARP Inhibition Shifts Murine Myeloid Cells Toward a More Tolerogenic Profile In Vivo
Year: 2025
Type: article
Abstract: The human Poly ADP-ribose Polymerase (PARP) family comprises 17 enzymes responsible for the transfer of ADP-ribose to proteins, forming poly- or mono-ADP-ribosylation. This post-translational modification regulates DNA repair and programmed cell death, processes affecting cancer biology. PARP inhibitors, including the FDA-approved olaparib, are used to treat BRCA-dependent breast and ovarian cancers. Although therapies with use of PARP inhibitors are showing clinical success, their effects on the immune system remain understudied. Prior work has shown that PARP inhibition can modulate inflammatory responses and alter innate immunity. In this study, we evaluated the immunomodulatory effects of olaparib on myeloid cells in vivo, focusing on bone marrow and spleen. Olaparib treatment altered the composition and activation state of dendritic cells, neutrophils, and macrophages. In the bone marrow, olaparib increased the proportion of cDC2 population, mature neutrophils and inflammatory macrophages expressing CD80. In contrast, splenic myeloid cells exhibited enhanced expression of markers associated with tolerogenic phenotypes, including CD206 and CD124 in neutrophils and macrophages. The spleen also showed an increase in immature monocyte-derived dendritic cells (CD206+) and a bias toward the cDC2 subset. These findings indicate that PARP inhibition can induce short-term phenotypic remodeling of myeloid cell populations, promoting a more immunoregulatory profile, especially in the spleen. These changes may contribute to an altered immune landscape with implications for anti-tumor immunity.
Source: Biomolecules
DOI: 10.3390/biom15081149
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W4413225353