Lack of differences in radiation-induced immunogenicity parameters between HPV-positive and HPV-negative human HNSCC cell lines

Radiother Oncol. 2017 Sep;124(3):411-417. doi: 10.1016/j.radonc.2017.08.018. Epub 2017 Sep 12.


Background and purpose: Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines.

Material and methods: Calreticulin (CRT) exposure was detected on cancer cell surface. ATP, HMGB1 and cytokines were measured in culture supernatants. Maturation marker CD83 surface exposure was determined on DCs after co-incubation with irradiated tumor cells.

Results: There was no increase in DAMPs and cytokine profiles after radiation treatment and no difference between HPV+ and HPV- cell lines. The HPV/p16-positive SCC90 cells showed a trend for increased total CRT, HMGB1, and number of cytokines compared to all other cell lines. None of the irradiated cancer cell lines could affect DC maturation.

Conclusions: Radiation treatment did not increase immunogenicity of HNSCC cell lines assessed by membrane CRT, ATP, HMGB1, cytokines production, and by activation of immature DCs. There was no difference between HPV-positive and HPV-negative cell lines.

Keywords: ATP; Calreticulin; Dendritic cell maturation; HMGB1; HNSCC; HPV.

MeSH terms

  • Calreticulin / immunology
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Carcinoma, Squamous Cell / virology
  • Cell Line, Tumor
  • Cytokines / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / radiation effects
  • Female
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / radiotherapy*
  • Head and Neck Neoplasms / virology
  • Humans
  • Male
  • Middle Aged
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / pathology
  • Squamous Cell Carcinoma of Head and Neck


  • CALR protein, human
  • Calreticulin
  • Cytokines