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CDK2 inhibition sensitizes anthracycline-induced immunogenic cell death and enhances the efficacy of anti-PD-1 therapy.


ABSTRACT:

Introduction

CDK2 (Cyclin-dependent kinase 2) is an oncogenic cyclin-dependent kinase with potent mitogenic and immunosuppressive functions. Despite extensive research on CDK2 inhibitors, the lack of selectivity has made it unclear whether CDK2 inhibition specifically facilitate immunogenic cell death.

Methods

We used CRISPR-Cas9 system to generate Cdk2-/- MCA205 cells. Tumor cells were inoculated subcutaneously into mice while administering MTX (mitoxantrone) or anti-PD-1 antibodies treatment to observe tumor growth curves. Next, immune cell infiltration in tumor microenvironment was detected by immunofluorescence. Furthermore, apoptosis pathway was evaluated by flow cytometry and western blot. The hallmarks of immunogenic cell death were detected by flow

SUBMITTER: Chen Y 

PROVIDER: S-EPMC12185487 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature