Disruption of cell-intrinsic PCSK9 enhances the antitumor efficacy of CD8⁺ T cells.

ABSTRACT:

Background

Tumor-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) facilitates tumor progression, but the role of immune cell-intrinsic PCSK9 in tumor control remains unclear.

Methods

Orthotopic models of pancreatic cancer and melanoma in Pcsk9-deficient mice were established and tumor-infiltrating immune cells were analyzed using single-cell RNA sequencing and flow cytometry. The effect of genetic disruptions of PCSK9 on murine CD8⁺ T cells and human chimeric antigen receptor (CAR)-T cells was evaluated both in vitro and in vivo.

Results

Ablation of host Pcsk9 remarkably suppressed tumor growth and prolonged the survival of tumor-bearing mice, while tumor cells still express PCSK9. The enhanced tumor suppression in Pcsk9-deficient

SUBMITTER: Liu B 

PROVIDER: S-EPMC12265815 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature