TCR-ζ EXPRESSION AND APOPTOSIS IN PERIPHRAL BLOOD MONONUCLEAR CELLS OF PATIENTS WITH HEAD AND NECK CANCER

头颈癌患者外周血单核细胞中 TCR-ζ 的表达和凋亡

• 批准号: 14571639
• 负责人: SAITO Takao
• 金额: $ 2.18万
• 依托单位: JIKEI UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571639/
• 关键词: HEAD AND NECK CANCER; APOPTOSIS; TCR-ζ; Fas-R; Fas-L; TUNEL ASSAY; PBMCs; TCR-ζ; sFas-L; TIL; 頭頸部扁平上皮癌; TNF-R1; Annexin-V; Caspase-3 assay

The decline of immunocompetence was often pointed out in patients with head and neck cancer. And the abnormality of signal transfer molecule in peripheral blood lymphocyte or tumor infiltrating lymphocyte, which was associated with T cell receptor(TCR) has been reported.We showed that the expression of TCR-ζ(T cell receptorζ), in CD4^+ T cells and CD8^+ T cerlls, was lower in patients with head and neck cancer than in control by quantitative flow cytometry. Moreover, by TUNEL assay(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ), which detected late phase apoptosis, the patients showed higher spontaneous apoptosis in CD3^+ T cell than normal control.On the other hand, the expression of Fas-R, which is one of the death receptors, on the surface of PBMCs(peripheral blood mononuclear cells) in patients with head and neck cancer was relatively high as compared with that in control. So the possibility of the apoptosis of PBMCs induced by Fas-Fas L complex as a mechanism of apoptosis without being connected with T cell receptor pathway was also guessed.

头颈部恶性肿瘤患者的免疫功能下降是常被提及的问题。我们用流式细胞术定量检测了头颈部恶性肿瘤患者外周血淋巴细胞或肿瘤浸润淋巴细胞中与T细胞受体（TCR）相关的信号传递分子的异常，发现头颈部恶性肿瘤患者外周血CD 4 ^+ T细胞和CD 8 ^+ T细胞中TCR-γ（TCR-γ）的表达均低于正常人。此外，通过TUNEL检测，采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法检测晚期凋亡，结果显示，与正常对照组相比，患者组CD 3 ^+ T细胞自发性凋亡明显增加。另一方面，死亡受体之一的Fas受体表达，头颈部癌患者外周血单个核细胞表面活性相对较高。由此推测，Fas-Fas L复合物诱导PBMC凋亡可能是一种与T细胞受体途径无关的凋亡机制。