Targeting PCSK9 Reduces Cancer Cell Stemness and Enhances Antitumor Immunity in Head and Neck Cancer

Overview

Journal iScience

Publisher Cell Press

Date 2023 Jun 12

PMID 37305703

Authors

Qi-Chao Yang

Shuo Wang

Yuan-Tong Liu

An Song

Zhi-Zhong Wu

Shu-Cheng Wan

Hui-Min Li

Zhi-Jun Sun

Affiliations

Soon will be listed here.

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been demonstrated to play a critical role in regulating cholesterol homeostasis and T cell antitumor immunity. However, the expression, function, and therapeutic value of PCSK9 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we found that the expression of PCSK9 was upregulated in HNSCC tissues, and higher PCSK9 expression indicated poorer prognosis in HNSCC patients. We further found that pharmacological inhibition or siRNA downregulating PCSK9 expression suppressed the stemness-like phenotype of cancer cells in an LDLR-dependent manner. Moreover, PCSK9 inhibition enhanced the infiltration of CD8 T cells and reduced the myeloid-derived suppressor cells (MDSCs) in a 4MOSC1 syngeneic tumor-bearing mouse model, and it also enhanced the antitumor effect of anti-PD-1 immune checkpoint blockade (ICB) therapy. Together, these results indicated that PCSK9, a traditional hypercholesterolemia target, may be a novel biomarker and therapeutic target to enhance ICB therapy in HNSCC.

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