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-1b, IL-2, IL-7, or a combination of IL-1b/IL-7) in vitro for the ability to expand tumour -infiltrating T lymphocytes (TIL) from individual patients (n ¼ 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 IFNg and TNFa 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.

Interleukin-8 and Interleukin-17 for Cancer

“…IL-7 values have been associated with bone metastatic disease and hematological malignancies [8][9][10]. Different levels of IL-7 have been measured in renal [11], neuroblastoma [12], glioma [13], colorectal [14], central nervous system, and lung cancers [15], however; until now no clear conclusions had been drawn in regards to how these values influence tumor progresIvyspring International Publisher sion. It has also been observed that IL-7 is responsible for osteoclastogenesis through fusion with macrophage colony stimulating factor (M-CSF), binding with tumor necrosis factor-α (TNF-α) and receptor activator of nuclear factor-α (RANKL) [16][17][18].…”

Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human neural progenitor cells

“…IL-7 has also been described to be alternatively spliced. [8][9][10][11] This is not driven by allelic variants of the human IL-7 gene, located on chromosome 8q12-13. IL-7 splice variants have been identified in different conditions: malignant transformation, 9 exposure to proinflammatory cytokines and tissue/organspecific expression.…”

Antigen-Driven T-Cell Selection in Patients with Cervical Cancer as Evidenced by T-Cell Receptor Analysis and Recognition of Autologous Tumor

“…Recent results suggested that IL-7 does not result in nonspecific alterations of the T-cell population but, rather, exerts a homeostatic effect by increasing the number of antigen-specific T cells (8). Therefore, differences in the TCR composition of TIL observed in this report may also reflect the antigen-driven expansion of certain TCR VA and VB subsets which may have already been selected for IL-7-dependent growth in vivo (20). In addition, gain of TIL effector function may not be correlated with expansion of certain TCR families (8).…”