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.
Steele
J C
JC
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. j.c.steele@bham.ac.uk
Mann
C H
CH
Rookes
S
S
Rollason
T
T
Murphy
D
D
Freeth
M G
MG
Gallimore
P H
PH
Roberts
S
S
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*