KLF7 promotes progression of Head and Neck Squamous Cell Carcinoma by remodeling tumor immune microenvironment

Area of Science:

• Oncology
• Cancer Immunology
• Molecular Biology

Background:

• Aberrant transcription factor (TF) activation drives cancer initiation and progression.
• Dysregulated TFs and their role in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment are poorly understood.
• Identifying novel oncogenic TFs is crucial for understanding HNSCC pathogenesis.

Purpose of the Study:

• To investigate the landscape of dysregulated oncogenic TFs in HNSCC.
• To elucidate the biological contributions of TFs to the HNSCC immune microenvironment.
• To identify potential therapeutic vulnerabilities in HNSCC.

Main Methods:

• Global investigation of oncogenic TF-target interactions in clinical HNSCC samples.
• In vitro and in vivo experiments to assess KLF-7's role in HNSCC progression and macrophage recruitment.
• Mechanistic studies to identify direct targets of KLF-7, including LOX.
• Analysis of extracellular matrix stiffness and its impact on immune cell function.
• Clinical correlation analysis of KLF-7, LOX, and TAMs in HNSCC.

Main Results:

• KLF-7 identified as a highly potential oncogenic TF in HNSCC.
• KLF-7 promotes HNSCC progression by governing autonomous malignant behaviors and recruiting tumor-associated macrophages (TAMs) in a TAM-dependent manner.
• LOX is a direct transcriptional target of KLF-7 in HNSCC cells.
• LOX-induced extracellular matrix stiffening promotes TAM recruitment and impairs CD8+ T cell-mediated killing.
• Significant clinical correlation found between KLF-7, LOX, and TAMs in HNSCC.

Conclusions:

• KLF-7 plays an extrinsic oncogenic role in HNSCC by remodeling the tumor immune microenvironment.
• The KLF-7/LOX/TAM signaling axis represents a novel mechanism promoting HNSCC progression.
• This signaling pathway offers a potential therapeutic vulnerability for HNSCC patients.