CD4+ T helper responses in squamous cell carcinoma of the head and neck.
Anti-tumor immunity plays an important role in the development of and protection from malignancy. However, there is a lack of information regarding induction of CD4+ T helper responses in patients with squamous cell carcinoma (SCCHN). To explore anti-tumor immune responses against SCCHN, a permanent cell line, Gun-1 was established from a squamous cell carcinoma of the hypopharynx. In addition to its characterization, we performed mixed lymphocyte-tumor cell cultures (MLTC) using peripheral blood lymphocytes and autologous tumor cells. Furthermore, T cell responses to wild type (wt) p53-derived peptides were assessed. Gun-1 cells overexpressed p53 and were negative for HLA-A2 expression. No tumor-specific or wt p53-specific CD8+ CTL lines could be established from peripheral blood mononuclear cells (PBMCs) of this patient. Autologous tumor-specific HLA-DR-restricted CD4+ T helper clone was obtained by limiting dilutions using bulk populations from MLTC. This clone produced IFN-gamma but not IL-5 in response to autologous tumor cells. In addition, CD4+ T cells were generated from the patient's PBMCs which responded to two HLA-DP5-restricted wt p53-derived peptides. Our results suggest that the immune cells specific for autologous tumor as well as wt p53-derived epitopes are present in the peripheral circulation of this cancer patient. However, helper-type CD4+ T lymphocytes represent the predominant anti-tumor response.
Chikamatsu
Kazuaki
K
Department of Otolaryngology - Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan. chikamatsu@yamanashi.ac.jp
Sakakura
Koichi
K
Yamamoto
Takanori
T
Furuya
Nobuhiko
N
Whiteside
Theresa L
TL
Masuyama
Keisuke
K
D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D016159:Tumor Suppressor Protein p53