Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor that originates from the squamous epithelial cells in the tissues of the head and neck, including the oral cavity, nasopharynx, oropharynx, lip, nasal cavity, paranasal sinuses, and salivary glands, and it represents the most common malignancies occurring in the head and neck region (Barsouk, Aluru, Rawla, Saginala, & Barsouk, 2023). Globally, HNSCC ranks seventh in terms of cancer prevalence, with approximately 890,000 new cases annually, which constitutes around 4.5 % of all cancer diagnoses worldwide. Additionally, it is responsible for about 450,000 fatalities per year, accounting for roughly 4.6 % of global cancer-related deaths (Barsouk et al., 2023). The principal modalities of therapy for HNSCC are surgical resection, radiation and systemic therapy, including chemotherapy, immunotherapy. However, HNSCC is an aggressive, genetically complex malignancy, with more than 60 % of HNSCC patients diagnosed at an advanced or metastatic stage of the disease. Primary and acquired treatment resistance is common and clinical outcomes of HNSCC remain poor (Alsahafi, 2019, Bray et al., 2018). More effective therapies need to be explored urgently.

The development of cancer is inextricably linked to the functional status of the immune system, which is deemed to recognize and eliminate abnormal cells, including those that may develop into cancerous cells (Gonzalez, Hagerling, & Werb, 2018). However, established cancer cells can evade immune surveillance through various mechanisms, such as reducing the expression of surface antigens and inhibiting the activity of immune cells (Messerschmidt, Prendergast, & Messerschmidt, 2016). Hence, in cancer treatment, activating and enhancing the immune system has emerged as a crucial strategy with immune checkpoint inhibitors (ICIs) showing tremendous progress in diverse solid tumors.

γδ T (γδ T) cells represent a unique subset within the immune system, distinct from the more common alpha-beta (αβ) T cells, and only constitute a small fraction of T cells (Pandya, Murray, Pollok, & Renbarger, 2016). γδ T cells can directly recognize and kill cancer cells that express tumor-associated antigens, modulate immune responses, promote the activation and proliferation of other immune cells, and produce various cytokines, such as interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), thereby inhibiting the growth and spread of cancer cells (Kabelitz et al., 2020, Yazdanifar et al., 2020). The role of γδ T cells in HNSCC has gained increasing attention as a potential therapeutic target, concurrent with the exploration of the immune system.