SKP2 inhibition activates tumor cell-intrinsic immunity by inducing DNA replication stress and genomic instability.

ABSTRACT:

Background

S-phase kinase-associated protein 2 (SKP2) is a typical oncogene aberrantly overexpressing in a variety of cancer types, but it remains elusive whether SKP2 regulates the antitumor immunity of triple-negative breast cancer.

Methods

The efficacy of anti-PD-1 was evaluated in the orthotopic xenografts of immunocompetent mice models. The infiltration of cytotoxic T cells in tumor microenvironment(TME) were assessed by immunofluorescence staining. The levels of pro-inflammatory chemokines were analyzed by ELISA. The protein interaction was analyzed by co-immunoprecipitation and GST pull-down. The genomic instability was analyzed by fluorescent microscopy.

Results

SKP2 inhibition significantly improved the antitumor efficacy of immune checkpoint blockade (ICB).

SUBMITTER: Peng Y 

PROVIDER: S-EPMC11723935 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature