T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia.
Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease.
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. j.c.steele@bham.ac.uk
J C
JC
Steele
C H
CH
Mann
S
S
Rookes
T
T
Rollason
D
D
Murphy
M G
MG
Freeth
P H
PH
Gallimore
S
S
Roberts
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology*