HPV infection related immune infiltration gene associated therapeutic strategy and clinical outcome in HNSCC

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common tumor in human. Research has shown that HPV status HNSCC is a unique prognosis factor, which may due to its immune infiltration landscape. But the underlying mechanism is unclear. METHODS: In this study, we used a combination of several bioinformatics tools, including WCGNA, ssGSEA, CIBERSORT, TIDE,etc., to explore significant genes both related to HPV infection status and immune cell infiltration in HNSCC patients. RESULTS: Combined with several bioinformatics algorithms, eight hub genes were identified, including LTB, CD19, CD3D, SKAP1, KLRB1, CCL19, TBC1D10C and ARHGAP4. In HNSCC population, the hub genes had a stable co-expression, which was related to immune cell infiltration, especially CD8+ T cells, and the infiltrative immune cells were in a dysfunctional status. Samples with high hub genes expression presented with better response to immune check point block (ICB) therapy and sensitivity to bleomycin and methotrexate. CONCLUSIONS: The eight hub genes we found presented with a stable co-expression in immune cell infiltration of HPV + ve HNSCC population. The co-expression of hub genes related to an immune microenvironment featuring an increase in immune cells but high degree of immune dysfunction status. Patients with high hub gene expression had a better response to ICB treatment, bleomycin and methotrexate. The co-expression of hub genes may be related to immune infiltration status in patients. The concrete molecular mechanism of hub genes function demands further exploration.