title: Decreased HPV-specific T cell responses and accumulation of immunosuppressive influences in oropharyngeal cancer patients following radical therapy.
abstract: 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.
authors.affiliation: Velindre Cancer Centre, Cardiff, UK.
authors.forename: Saly
authors.initials: S
authors.lastname: Al-Taei
authors.forename: Russell
authors.initials: R
authors.lastname: Banner
authors.forename: Ned
authors.initials: N
authors.lastname: Powell
authors.forename: Mererid
authors.initials: M
authors.lastname: Evans
authors.forename: Nachi
authors.initials: N
authors.lastname: Palaniappan
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Tabi
authors.forename: Stephen
authors.initials: S
authors.lastname: Man
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000628:therapy / Q000821:virology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007156:Immunologic Memory; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D009959:Oropharyngeal Neoplasms / Q000276:immunology* / Q000628:therapy / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D007371:Interferon-gamma