Effect of human papillomavirus-16 infection on CD8+ T-cell recognition of a wild-type sequence p53264-272 peptide in patients with squamous cell carcinoma of the head and neck

Abstract

Purpose: Wild-type sequence (wt) p53 peptides are attractive candidates for broadly applicable cancer vaccines, currently considered primarily for patients whose tumors overexpress p53. Circumstances exist, however, where increased p53 degradation may result in appreciable presentation of p53-derived peptides, despite low p53 expression. Squamous cell carcinoma of the head and neck is associated with oncogenic human papillomavirus (HPV) subtypes, which inactivate p53 through proteasomal degradation. The criterion of p53 overexpression would exclude these individuals from wt p53-based immunotherapy.

Experimental design: We tested the correlation of HPV infection with enhanced antigenicity of the p53 protein and postulated that removal of HPV-16(+) tumors with enhanced p53(264)-(272) peptide presentation might lead to a drop in T cells specific for this peptide in vivo. Circulating frequencies of T cells specific for the HLA A*0201:p53(264)-(272) complex were measured ex vivo using dimeric HLA:peptide complexes in 15 head and neck cancer patients before and 6 months after tumor excision.

Results: CD8+ T-cell recognition of HLA A*0201 restricted wt p53(264)-(272) peptide presented by HPV-16(-) squamous cell carcinoma of the head and neck lines was enhanced by HPV-16 E6 expression, sometimes exceeding that of a naturally transformed, HPV-16(+) wt p53 expressing squamous cell carcinoma of the head and neck cell line. In patients with HPV-16(-) tumors, the frequency of wt p53(264-272)-specific T cells remained largely unchanged after tumor removal. However, a significant decline in frequency of anti-p53(264-272) T cells was observed postoperatively in HPV-16(+) patients (P < 0.005).

Conclusions: Recognition of HPV-associated squamous cell carcinoma of the head and neck appears associated with levels of wt p53-specific T cells and inversely with p53 expression. p53 peptides may be useful tumor antigens for squamous cell carcinoma of the head and neck immunotherapy in addition to viral gene products.