Local expression of cytokines in human colorectal carcinoma: Evidence of specific interleukin-6 gene expression

Local expression of cytokines in human colorectal carcinoma: Evidence of specific interleukin-6 gene expression
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DOI:
10.1097/00002371-199901000-00004
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发表时间:
1999-01-01
影响因子:
3.9
通讯作者:
Casciani, CU
Casciani, CU
中科院分区:
医学4区
文献类型:
--
作者:
Piancatelli, D;Romano, P;Casciani, CU

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研究人员对 12 名接受手术切除的结直肠癌患者的肿瘤组织、正常粘膜和外周血单核细胞 (PBMC) 中细胞因子 mRNA 的表达进行了研究,以表征局部免疫状况。使用逆转录酶聚合酶链式反应 (RT-PCR) 技术检测白细胞介素 (n)-1 beta、IL-2、IL-2-R(p55)、IL-4、IL-5、IL-6 和 IL-10 的 mRNA 转录本。 IL-6 mRNA 在 83% 的病例中在肿瘤组织中表达,但只有 1 例在正常粘膜中表达(p < 0.001);血清IL-6水平与IL-6 mRNA无相关性;所有肿瘤组织样本中均存在 IL-1 β 转录物;未检测到IL-4表达; IL-2 mRNA 仅存在于两种肿瘤中; IL-2R(p55) mRNA 在 58% 的肿瘤中发现,但在正常粘膜中未发现 (p = 0.005)。 IL-10的表达表明它在结直肠癌免疫抑制中不发挥核心作用,并且PBMC中的细胞因子表达表明不同且独立的激活。这项研究表明肿瘤微环境中炎症细胞因子的表达模式,可能是由浸润的免疫细胞产生的。特异性免疫激活细胞因子 IL-2 和 IL-4 的缺乏可能表明抗癌免疫反应受损; IL-2R 结果证实了 IL-2/IL-2R 激活途径的失调。这些发现可能有助于更好地了解细胞因子,尤其是 IL-6 在肿瘤部位的作用,以及它们在开发有效免疫疗法中的重要性。
The expression of cytokine mRNAs in tumor tissue, normal mucosa, and peripheral blood mononuclear cells (PBMCs) was studied in 12 patients with colorectal cancer undergoing surgical resection, to characterize local immune conditions. mRNA transcripts for interleukin (n)-1 beta, IL-2, IL-2-R(p55), IL-4, IL-5, IL-6, and IL-10 were detected using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. IL-6 mRNA was expressed in tumor tissue in 83% of the cases but only in one case in normal mucosa (p < 0.001); serum levels of IL-6 did not show any correlation with IL-6 mRNA; IL-1 beta transcripts were present in all tumor tissue samples; no IL-4 expression was detected; IL-2 mRNA was only present in two tumors; IL-2R(p55) mRNA was found in 58% of tumors but not in normal mucosae (p = 0.005). The expression of IL-10 suggests that it does not play a central role in colorectal cancer immunosuppression, and cytokine expression in PBMCs indicates a different and independent activation. This study suggests a pattern of expression of inflammatory cytokines in the tumor microenvironment, probably produced by infiltrating immune cells. The absence of the specific immune-activating cytokines, IL-2 and IL-4, could indicate an impairment of the anticancer immune response; IL-2R results confirm the dysregulation of the IL-2/IL-2R activation pathway. These findings may lead to a better understanding of the role of cytokines and especially IL-6 at the tumor site and hence their importance in developing an effective immunotherapy.