Establishment and validation of a tumor-infiltrating γδT cell related prognostic gene signature in head and neck squamous cell carcinoma

gamma delta T cells are unconventional T cells only accounting for 1-5 % of circulating T lymphocytes. Their potent antitumor capability has been evidenced by accumulating studies. However, the prognostic value of gamma delta T cells remains not well documented in head and neck squamous cell carcinoma (HNSCC). In this study, we utilized the TCGA HNSCC database to evaluate the infiltration of gamma delta T cells and the association between gamma delta T cells and clinicopathological factors by related gene signature, which were then validated by a total of 100 collected tumor samples from HNSCC patient cohort. Heterogeneity and functional characteristics of distinct infiltrating gamma delta T cell profiles in HNSCC were then investigated based on the scRNA-seq data from the GEO database. We found higher gamma delta T cell gene signature score was significantly associated with longer survival. Cox regression models showed that gamma delta T cell gene signature could serve as an independent prognostic indicator for HNSCC patients. A high level of gamma delta T cell-related gene signature was positively correlated with the infiltration of tumor-infiltrating lymphocytes and immune score. Through scRNA-seq analysis, we identified that gamma delta+ Trm cells and gamma delta+ CTL cells possessed anti-tumor and immunoregulatory properties. Notably, we found a significant association between the presence of these cells and improved survival outcomes. In our cell-cell communication analyses, we identified that gamma delta T cells have the potential to eliminate tumor cells through the secretion of interferon-gamma and granzyme. Collectively, the infiltration of gamma delta T cells may serve as a promising prognostic tool, prompting the consideration of treatment options for patients with HNSCC.