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

BMC Cancer. 2020 Aug 24;20(1):796. doi: 10.1186/s12885-020-07298-y.

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 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.

Keywords: Gene; HNSCC; HPV; Immunotherapy; Tumor microenvironment.

MeSH terms

  • Alphapapillomavirus / immunology
  • Alphapapillomavirus / isolation & purification
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / pharmacology
  • Bleomycin / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology
  • Computational Biology
  • Datasets as Topic
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / immunology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Methotrexate / pharmacology
  • Methotrexate / therapeutic use
  • Oligonucleotide Array Sequence Analysis
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / virology
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Squamous Cell Carcinoma of Head and Neck / virology
  • Transcriptome / immunology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Immune Checkpoint Inhibitors
  • Bleomycin
  • Methotrexate