Tumor-associated neutrophil precursors impair homologous DNA repair and promote sensitivity to PARP inhibition.

ABSTRACT: Tumor evolution is one of the major mechanisms responsible for acquiring therapy-resistant and more aggressive cancer clones. Whether the tumor microenvironment through immune-mediated mechanisms might promote the development of more aggressive cancer types is crucial for the identification of additional therapeutic opportunities. Here, we identify a subset of tumor-associated neutrophils, defined as tumor-associated neutrophil precursors (PreNeu). These PreNeu are enriched in highly proliferative hormone-dependent breast cancers and impair DNA repair capacity. Mechanistically, succinate secreted by tumor-associated PreNeu inhibits homologous recombination, promoting error-prone DNA repair through non-homologous end-joining regulated by PARP-1. Consequently, breast cancer cells acquire gen

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC12310969 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature