Identification of Interleukin‐Related Genes Signature for Prognosis Prediction in Head and Neck Squamous Cell Carcinoma Patients

This study focused on identifying the interleukin (IL)-related genes that influence the head and neck squamous cell carcinoma (HNSCC) patients' prognosis and response to anticancer therapy in patients with HNSCC. We developed a risk model that included three gene signatures, IL Enhancer Binding Factor 2 (ILF2), IL 36 alpha (IL36A), and IL10, based on differential expression analysis, survival analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and Cox regression analysis. We found that the low-risk group was scored with higher immune cell infiltration, higher expression of human leukocyte antigen (HLA) family genes and immune checkpoint genes, higher cytolytic activity (CYT), tertiary lymphoid structures (TLS), and CD8A/PD-L1 ratio. In contrast, the high-risk group was scored with higher tumor immune dysfunction and exclusion (TIDE), which implied worse response to immunotherapy and worse prognosis. The results above indicated that the low-risk group had stronger antitumor immunity and better responsiveness to immunotherapy. We also observed a significantly enriched pattern of cancer-related pathways and immune pathways in the comparison of the high-risk and low-risk groups. Furthermore, the high-risk group had higher sensitivity to chemotherapy drugs, which suggested that they might benefit from chemotherapy treatment. Following the results above, we confirmed in HNSCC cell lines and clinical specimens that the level of ILF2 in tumors was significantly higher than that in adjacent tumor tissues. Besides, in vivo and in vitro results both showed that silencing ILF2 might depress tumor growth, invasion, and migration. This study not only provided novel perspectives into the immunological and molecular mechanisms of HNSCC and uncovered IL-related gene signatures for predicting HNSCC patients' prognosis and response to chemotherapy and immunotherapy, but also preliminarily suggested that ILF2 might be an important target in the treatment of HNSCC.