title: Interleukin-7 (IL-7) in colorectal cancer: IL-7 is produced by tissues from colorectal cancer and promotes preferential expansion of tumour infiltrating lymphocytes.
abstract: 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.
authors.affiliation: Department of Surgery, University of Pittsburgh Medical School, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Maeurer
authors.forename: W
authors.initials: W
authors.lastname: Walter
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: L
authors.initials: L
authors.lastname: Zitvogel
authors.forename: E
authors.initials: E
authors.lastname: Elder
authors.forename: W
authors.initials: W
authors.lastname: Storkus
authors.forename: M T
authors.initials: MT
authors.lastname: Lotze
mesh_terms: D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000276:immunology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D015342:DNA Probes / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015342:DNA Probes; D018076:DNA, Complementary; D007375:Interleukin-1; D007376:Interleukin-2; D015851:Interleukin-7; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma