Chikamatsu Kazuaki, Sakakura Koichi, Yamamoto Takanori, Furuya Nobuhiko, Whiteside Theresa L, Masuyama Keisuke
Department of Otolaryngology - Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.
Oral Oncol. 2008 Sep;44(9):870-7. doi: 10.1016/j.oraloncology.2007.11.001. Epub 2008 Jan 24.
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.
抗肿瘤免疫在恶性肿瘤的发生发展及防护中发挥着重要作用。然而，关于鳞状细胞癌（SCCHN）患者中CD4 + T辅助细胞应答的诱导情况，目前尚缺乏相关信息。为了探究针对SCCHN的抗肿瘤免疫应答，我们从一名下咽鳞状细胞癌患者中建立了一个永生化细胞系Gun-1。除了对其进行特性鉴定外，我们还使用外周血淋巴细胞和自体肿瘤细胞进行了混合淋巴细胞 - 肿瘤细胞培养（MLTC）。此外，我们评估了T细胞对野生型（wt）p53衍生肽的应答。Gun-1细胞过表达p53，且HLA - A2表达呈阴性。从该患者的外周血单核细胞（PBMC）中未能建立肿瘤特异性或wt p53特异性的CD8 + CTL系。通过对MLTC中的大量细胞进行有限稀释，获得了自体肿瘤特异性的HLA - DR限制性CD4 + T辅助细胞克隆。该克隆在受到自体肿瘤细胞刺激时产生IFN - γ，但不产生IL - 5。此外，从患者的PBMC中产生了对两种HLA - DP5限制性wt p53衍生肽有应答的CD4 + T细胞。我们的结果表明，该癌症患者外周循环中存在针对自体肿瘤以及wt p53衍生表位的免疫细胞。然而，辅助型CD4 + T淋巴细胞代表了主要的抗肿瘤应答。
