Maeurer M J, Walter W, Martin D, Zitvogel L, Elder E, Storkus W, Lotze M T
Department of Surgery, University of Pittsburgh Medical School, USA.
Scand J Immunol. 1997 Feb;45(2):182-92. doi: 10.1046/j.1365-3083.1997.d01-384.x.
Despite increasing survival rates for patients with colorectal cancer, additional treatment options are required, including active or passive immunotherapy for patients with metastatic disease. Freshly harvested colorectal cancer specimens and in vitro cultured colorectal cancer cell lines were examined for IL-7 protein secretion in order to examine the potential role of this cytokine in the interaction between tumour cells and the host immune system. Freshly harvested colorectal cancer specimens (21/21), or normal adjacent mucosa (3/3), as well as long-term established colorectal cancer cell lines (3/4) exhibited IL-7 mRNA expression as detected by RT-PCR and confirmed by Southern Blot analysis. Freshly harvested colorectal cancer tissue (16/18), or long-term established colorectal cancer cell lines (2/4) secreted in vitro IL-7 as detected by ELISA. In contrast, breast, pancreatic, or lung cancer cell lines, as well as several haematopoietic cancer cells lines, tested negative for IL-7 mRNA and protein. The authors tested different cytokines (IL-1 beta, IL-2, IL-7, or a combination of IL-1 beta/IL-7) in vitro for the ability to expand tumour-infiltrating T lymphocytes (TIL) from individual patients (n = 9) with colorectal cancer. TIL populations were tested at day 14 after in vitro propagation for phenotypic analysis by FACS and for reactivity directed against NK and LAK sensitive target cells and autologous cancer cells as measured by cytotoxicity and cytokine release. TIL obtained from colorectal cancer lesions can be efficiently expanded in the presence of IL-7, some(3/9) of which appear to exhibit autologous tumour recognition as measured by cytolytic effector functions and by detection of IFN gamma and TNF alpha release. Detection of IL-7 mRNA expression in colorectal cancer, in normal mucosa adjacent to tumour, as well as the ability of colorectal cancer tissue to secrete IL-7, raises new questions about the biology of the host/tumour interactions in colorectal cancer.
尽管结直肠癌患者的生存率在不断提高,但仍需要更多的治疗选择,包括针对转移性疾病患者的主动或被动免疫疗法。为了研究这种细胞因子在肿瘤细胞与宿主免疫系统相互作用中的潜在作用,对新鲜采集的结直肠癌标本和体外培养的结直肠癌细胞系进行了IL-7蛋白分泌检测。通过逆转录聚合酶链反应(RT-PCR)检测并经Southern印迹分析证实,新鲜采集的结直肠癌标本(21/21)或正常相邻黏膜(3/3)以及长期建立的结直肠癌细胞系(3/4)均表现出IL-7 mRNA表达。通过酶联免疫吸附测定(ELISA)检测发现,新鲜采集的结直肠癌组织(16/18)或长期建立的结直肠癌细胞系(2/4)在体外分泌IL-7。相比之下,乳腺癌、胰腺癌或肺癌细胞系以及几种造血癌细胞系的IL-7 mRNA和蛋白检测均为阴性。作者在体外测试了不同的细胞因子(IL-1β、IL-2、IL-7或IL-1β/IL-7组合)对来自9例结直肠癌个体患者的肿瘤浸润性T淋巴细胞(TIL)的扩增能力。体外培养14天后,对TIL群体进行流式细胞术(FACS)表型分析,并通过细胞毒性和细胞因子释放检测其针对NK和LAK敏感靶细胞以及自体癌细胞的反应性。在IL-7存在的情况下,从结直肠癌病变中获得的TIL可以有效扩增,其中一些(3/9)通过溶细胞效应功能以及检测IFNγ和TNFα释放显示出对自体肿瘤的识别能力。在结直肠癌、肿瘤相邻的正常黏膜中检测到IL-7 mRNA表达以及结直肠癌组织分泌IL-7的能力,引发了关于结直肠癌中宿主/肿瘤相互作用生物学的新问题。