γδ17T Cells Aggravate Carcinogen-Induced Oral Squamous Cell Carcinoma

Area of Science:

• Immunology
• Oncology
• Cancer Biology

Background:

• Oral squamous cell carcinoma (OSCC) is an aggressive cancer with poor survival rates and frequent metastasis.
• Gamma delta T (γδT) cells possess both innate and adaptive immune functions, exhibiting context-dependent anti- or pro-tumor roles in cancer.
• Understanding the specific role of γδT cells in OSCC is crucial for developing effective therapeutic interventions.

Purpose of the Study:

• To investigate the role of γδT cells in the development and progression of oral squamous cell carcinoma (OSCC).
• To elucidate the mechanisms by which γδT cells influence tumor growth and the tumor microenvironment in OSCC.
• To determine the contribution of IL-17-producing γδT cells to OSCC progression and angiogenesis.

Main Methods:

• Utilized a 4-nitroquinoline-1-oxide (4NQO)-induced murine model of OSCC to mimic human disease progression.
• Characterized γδT cell populations in the tongue epithelium, the primary cancer site in the model.
• Assessed the impact of γδT cell depletion and IL-17 deficiency on OSCC tumor growth, kinetics, and the oral microbiota.

Main Results:

• Depletion of γδT cells reduced OSCC tumor size and number, indicating a pro-tumorigenic role.
• Absence of IL-17, a key cytokine from Vγ6+ γδT cells, also led to reduced tumor volume, confirming a pro-tumorigenic function.
• IL-17-producing γδT cells promote tumor angiogenesis by increasing angiogenic factor expression, independent of oral microbiota changes.

Conclusions:

• IL-17-producing γδT cells play a pathologic role in OSCC by promoting tumor growth through angiogenesis.
• The pro-tumorigenic effects of these γδT cells in OSCC are independent of alterations in the oral microbiota.
• Targeting γδT cells, particularly IL-17-producing subsets, represents a potential therapeutic strategy for oral squamous cell carcinoma.