title: CD4+ T cell responses to HLA-DP5-restricted wild-type sequence p53 peptides in patients with head and neck cancer.
abstract: Wild-type sequence (wt) p53 peptides are attractive candidates for broadly applicable cancer vaccines. Evidence has been accumulating which indicates that CD4+ Th cells have an important role in generating and maintaining antitumor immune responses. To elucidate the nature of CD4+ Th responses to wt p53 epitopes in patients with squamous cell carcinoma of the head and neck (SCCHN), peripheral blood mononuclear cells (PBMCs) from HLA-DP5+ patients were stimulated with HLA-DP5-restricted wt p53 peptides, p53(108-122) or p53(153-166), and tested for the release of IFN-gamma and IL-5 in ELISPOT assays. Immunohistochemistry for p53 accumulation in tumors, and ELISA for serum antibodies to p53 were also performed. Eleven (57.9%) of 19 HLA-DP5+ patients but none of 5 healthy donors had detectable Th1 and/or Th2 responses to wt p53 peptides by ELISPOT assay. Among these 11 responding patients, 9 (81.8%) and all 11 (100%) patients had a tumor burden and p53 accumulation, respectively. On the other hand, two responding patients were in post-operative condition. Interestingly, among nine patients with a tumor burden, four patients with early disease showed either Th1-polarized or mixed Th1/Th2 responses, while five patients with advanced disease showed either Th2-polarized or mixed Th1/Th2 responses. Our results suggest that wt p53(108-122) and p53(153-166) peptides stimulate both Th1- and Th2-type CD4+ T cell responses in patients with SCCHN, and anti-p53 Th responses may persist even after surgical resection of the tumor; however, the presence of a tumor and its progression may affect the nature of immune responses to wt p53 peptides.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan. chikamatsu@yamanashi.ac.jp
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chikamatsu
authors.forename: Koichi
authors.initials: K
authors.lastname: Sakakura
authors.forename: Goro
authors.initials: G
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okamoto
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Furuya
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: Albert B
authors.initials: AB
authors.lastname: DeLeo
authors.forename: Keisuke
authors.initials: K
authors.lastname: Masuyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006682:HLA-DP Antigens / Q000276:immunology* / Q000378:metabolism; D059868:HLA-DP beta-Chains; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma; D015848:Interleukin-5; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C538744:HLA-DPB1*05:01 antigen; D015848:Interleukin-5; D010446:Peptide Fragments; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C069261:interferon gamma (1-39); D007371:Interferon-gamma