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

Abstract

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 coexpression, 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.

Identification of Potential Key Biomarkers of Atrial Fibrillation and Their Correlation with Immune Infiltration in Atrial Tissue

“…Analysis. We quantified the infiltration levels for each immune cell type by single-sample gene set enrichment analysis (ssGSEA) in the R package GSVA [19]. The ssGSEA utilized the scoring result for individual samples.…”

Loss of BLK expression as a potential predictor of poor prognosis and immune checkpoint blockade response in NSCLC and contribute to tumor progression

“…We found that CCL19 (AUC=0.7850) showed the best predictive value for immunotherapy in LUSC. Previous study shown that high expression of CCL19 had a better response to ICB therapy in patients with HNSCC [37] , and the CCL19 high expression was related to immune cells infiltration and microenvironment featuring in the tumor [ 38 , 39 ]. These results explore mechanistic insights into the response to ICB, revealing that the antitumor effects of CCL19 were increased by additional treat with anti-PD-L1 antibody [40] .…”

Single-Cell Transcriptome Analysis Reveals Different Immune Signatures in HPV- and HPV + Driven Human Head and Neck Squamous Cell Carcinoma

“…CD19-positive B-cells were reported to be related to better response of PD-1 blockade in HPVassociated HNSCC and thus with improved survival [77]. Another study revealed CD19 to be one hub gene in HPVrelated HNSCC, predisposing for a better therapy response and clinical outcome [12]. In addition, the presence of respective B-cells in tumor draining lymph nodes was related to better prognosis in HNSCC [78].…”

“…Altogether, the understanding of HPV-positive HNSCC, related genetic mechanisms and risk prediction is of high clinical interest to improve the understanding of pathogenesis and to choose the appropriate therapy. Thereby, different studies aimed in the detection of potential hub genes in this context [4,6,7,10,[12][13][14][15]. Improving the knowledge on and understanding of the potential role of HPV integration in HNSCC biology appears thereby fundamental with regard to the design of new therapeutic strategies and selection of patients for individual therapeutic measure [4].…”