Department of General-, Visceral-, Vascular and Pediatric Surgery, University of Wuerzburg Hospital, Germany.
Cell Oncol (Dordr). 2011 Aug;34(4):315-26. doi: 10.1007/s13402-011-0027-7.
The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis.
Expression of Tumor necrosis factor-alpha (TNF-α) was analyzed in colorectal cancer specimen and the cancer cell line HT-29 by immunohistochemistry and RT-PCR. TNF-α expression on protein and mRNA level were correlated with clinical characteristics and impact on survival. TNFR-1 was co-labelled with TNF-α and CD8+ cytotoxic T cells in immunofluorescence double staining experiments.
94% (n = 98/104) of the patients with CRC expressed TNF-α. High TNF-α expression was significantly associated with positive lymph node stage and recurrence of the tumor. Multivariate analysis revealed high TNF-α expression as an independent prognostic factor. Immunohistochemistry was correlated with RT-PCR results (т = 0.794). Immunofluorescence double staining experiments revealed increased TNFR-1 expression by CD8+ cells.
TNF-α expression by tumor cells may be an efficient immunological escape mechanism by inflammation-enhanced metastases and probably by induction of apoptosis in tumor-infiltrating CD8+ immune cells resulting in a down regulation of the tumoral immune response. Our data support the role of tumor-derived TNF-α expression as an important promoter of tumoral immune escape mechanisms and malignant progression, and suggest that analysis on either protein (immunohistochemistry) or RNA level (RT-PCR) can be used effectively in this respect. Targeting TNF-α may be a promising option, especially in cases with high TNF-α expression and positive lymph node metastases.
恶性肿瘤的不断生长伴随着免疫反应的下降，其机制尚不清楚。肿瘤释放的细胞因子诱导细胞凋亡和炎症被认为在结直肠癌变中起重要作用，作为肿瘤逃逸机制。
通过免疫组织化学和 RT-PCR 分析结直肠癌标本和 HT-29 癌细胞系中肿瘤坏死因子-α（TNF-α）的表达。TNF-α 在蛋白和 mRNA 水平的表达与临床特征和生存影响相关。在免疫荧光双染色实验中，TNFR-1 与 TNF-α和 CD8+细胞毒性 T 细胞共同标记。
94%（n=98/104）的 CRC 患者表达 TNF-α。高 TNF-α 表达与阳性淋巴结分期和肿瘤复发显著相关。多变量分析显示高 TNF-α表达是独立的预后因素。免疫组织化学与 RT-PCR 结果相关（т=0.794）。免疫荧光双染色实验显示 CD8+细胞中 TNFR-1 表达增加。
肿瘤细胞表达 TNF-α可能是一种有效的免疫逃逸机制，通过炎症增强转移，可能通过诱导肿瘤浸润的 CD8+免疫细胞凋亡，从而下调肿瘤免疫反应。我们的数据支持肿瘤源性 TNF-α表达作为肿瘤免疫逃逸机制和恶性进展的重要促进因子的作用，并表明在这方面分析蛋白质（免疫组织化学）或 RNA 水平（RT-PCR）都可以有效使用。靶向 TNF-α可能是一种有前途的选择，特别是在 TNF-α 表达高和淋巴结转移阳性的情况下。
