Interleukin-7 (IL-7) in colorectal cancer: IL-7 is produced by tissues from colorectal cancer and promotes preferential expansion of tumour infiltrating lymphocytes

被引:55
作者
Maeurer, MJ
Walter, W
Martin, D
Zitvogel, L
Elder, E
Storkus, W
Lotze, MT
机构
[1] Depts. Surg., Biochem., Molec. G., Univ. of Pittsburgh Medical School
[2] Univ. of Pittsburgh Cancer Institute, Univ. of Pittsburgh Medical School
[3] Department of Medical Microbiology, University of Mainz, Mainz
[4] Department of Medical Microbiology, Johannes Gutenberg-Univ. of Mainz, 55101 Mainz, Hochhaus Augustusplatz
关键词
D O I
10.1046/j.1365-3083.1997.d01-384.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 FAGS 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 iv 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.
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页码:182 / 192
页数:11
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