Decreased HPV-specific T cell responses and accumulation of immunosuppressive influences in oropharyngeal cancer patients following radical therapy

Cancer Immunol Immunother. 2013 Dec;62(12):1821-30. doi: 10.1007/s00262-013-1488-5. Epub 2013 Oct 22.


Oropharyngeal cancer (OPC) is a type of squamous cell head and neck cancer that is often associated with human papillomavirus (HPV) infection, suggesting the potential for immunotherapeutic targeting of HPV antigens. This study aimed to determine the effect of radical therapy on HPV-specific T cells and other immune parameters in 20 OPC patients, as a prelude to future immunotherapy studies. HPV DNA could be detected in 9/12 available tissue samples (8/9 HPV(+) samples were also p16(+)). HPV-specific T cell responses against HPV16 E6 and E7 peptides were detected by enzyme-linked immunoSPOT in 10/13 and 8/13 evaluable patients, respectively, but did not appear to correlate with HPV status. Post-treatment, both HPV E6 and E7 T cell responses were decreased (4/13 and 2/13 patients, respectively). These reductions in T cell response could not be explained by a concurrent decrease in memory T cells whose absolute numbers were relatively unaffected by radical therapy (27,975 vs. 25,661/10(5) PBMC) despite a significant decrease in overall lymphocyte counts (1.74 vs. 0.69 × 10(9)/L). Instead, there were significant increases in regulatory T cells (3.7 vs. 6.8 %) and a population of myeloid-derived suppressor cells (CD14(-)HLA-DR(-)CD15(hi), 12.38 vs. 21.92 %). This suggests that immunosuppression may contribute to the reduction in HPV-specific T cell responses post-treatment, although study of larger patient cohorts will be required to test whether this affects clinical outcome. Overall these findings suggest that HPV-targeted immunotherapy in post-therapy OPC patients will require multiple strategies to boost T cell immunity and to overcome the influence of immunosuppressive cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / therapy
  • Carcinoma, Squamous Cell / virology
  • Cell Proliferation
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / immunology*
  • Humans
  • Immunoenzyme Techniques
  • Immunologic Memory
  • Immunotherapy
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Myeloid Cells / virology
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology
  • Oropharyngeal Neoplasms / immunology*
  • Oropharyngeal Neoplasms / therapy
  • Oropharyngeal Neoplasms / virology
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / immunology
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / therapy
  • Papillomavirus Infections / virology
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / virology


  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • Interferon-gamma