PD-1 Carried on Small Extracellular Vesicles Leads to OSCC Metastasis

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Programmed cell death protein 1 (PD-1) is a key immune checkpoint molecule impacting T cell activation and crucial in oral squamous cell carcinoma (OSCC) progression.
• Small extracellular vesicles (sEVs) carrying PD-1 (sEV PD-1) are implicated in tumor immunity, but their specific role in OSCC remains largely undefined.

Purpose of the Study:

• To investigate the biological functions and underlying mechanisms of sEV PD-1 in oral squamous cell carcinoma (OSCC).
• To explore the potential of targeting sEV PD-1 as a therapeutic strategy for OSCC.

Main Methods:

• In vitro experiments assessed cell cycle, proliferation, apoptosis, migration, and invasion of CAL27 cells treated with sEV PD-1.
• Mass spectrometry was employed to elucidate biological pathways.
• Immunohistochemical analysis was performed on xenograft mice models and OSCC patient samples.

Main Results:

• In vitro, sEV PD-1 induced senescence and epithelial-mesenchymal transition (EMT) in CAL27 cells via PD-L1 ligation and p38 MAPK pathway activation.
• Immunohistochemistry revealed a strong correlation between circulating sEV PD-1 levels and lymph node metastasis in OSCC.
• sEV PD-1 was shown to trigger senescence-initiated EMT in a PD-L1-p38 MAPK-dependent manner, promoting tumor metastasis.

Conclusions:

• Circulating sEV PD-1 plays a significant role in OSCC metastasis by inducing senescence and EMT.
• Targeting sEV PD-1 presents a promising therapeutic avenue for managing OSCC progression and metastasis.