PAK4 inhibition augments anti-tumour effect by immunomodulation in oral squamous cell carcinoma

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Oral squamous cell carcinoma (OSCC) is a prevalent malignancy requiring new therapeutic strategies.
• p21 activated kinase 4 (PAK4) is implicated in cancer progression and presents a potential therapeutic target.

Purpose of the Study:

• To evaluate the anti-tumour and immunomodulatory effects of PAK4 inhibition in OSCC.
• To investigate the impact of PAK4 inhibition on immune cell populations and T-cell responses in OSCC models.

Main Methods:

• Assessed PAK4 expression in OSCC cell lines and clinical samples.
• Utilized in vitro assays to analyze OSCC cell proliferation and apoptosis following PAK4 inhibition.
• Administered a PAK4 inhibitor in vivo to OSCC-bearing mice to study immune cell distribution and T-cell activation.
• Co-cultured dendritic cells (DCs) with T-cells to assess immune cell interactions.

Main Results:

• PAK4 was ubiquitously expressed in OSCC cells and tissues.
• PAK4 inhibition decreased OSCC cell proliferation and induced apoptosis.
• In vivo PAK4 inhibition suppressed tumour growth and increased IFN-γ-producing CD8+ T-cells.
• PAK4 inhibition enhanced DC numbers and co-stimulatory molecule expression, leading to augmented CD8+ T-cell activation.

Conclusions:

• PAK4 inhibition exerts direct anti-tumour effects in OSCC.
• PAK4 inhibition modulates the immune system to enhance anti-tumour immunity.
• Targeting PAK4 represents a potential therapeutic approach for OSCC treatment.