Interleukin-7 | IL7

  • IL7 is a hematopoietic growth factor secreted by stromal cells in the red marrow and thymus. It is also produced by keratinocytes, dendritic cells, hepatocytes, neurons, and epithelial cells but is not produced by lymphocytes.

  • IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic stem cells into lymphoid progenitor cells. It also stimulates proliferation of all cells in the lymphoid lineage (B cells, T cells and NK cells). It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and homeostasis. IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. IL-7 binds to the IL-7 receptor, a heterodimer consisting of Interleukin-7 receptor alpha and common gamma chain receptor. Il-7 promotes hematological malignacies (acute lymphoblastic leukemia, T cell lymphoma).

  • Viral Infections - Elevated levels of IL-7 have also been detected in the plasma of HIV-infected patients.

  • IL-7 as an immunotherapy agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during HIV infection. IL-7 could also be beneficial in improving immune recovery after allogenic stem cell transplant. Associated with antiretroviral therapy, IL-7 administration decreased local and systemic inflammations in patients that had incomplete T-cell reconstitution. These results suggest that IL-7 therapy can possibly improve the quality of life of those patients

  • Cancer - Elevated IL-7 promotes hematological malignancies (acute lymphoblastic leukemia, T cell lymphoma). IL-7 can be produced by some human tumour cells.

  • IL7 Tumour development and progression.

  • IL-7 is a well established as a proliferative and trophic cytokine that induces the development and proliferation of haematopoietic cells and malignancies.

  • Recently, several publications have demonstrated the expression of IL-7 receptor in non-haematopietic neoplasms (Saito et al., 1997; Yamada et al., 1997). It is proposed that IL-7 might have some indirect effects on tumourigenesis via regulating some intracellular mechanisms, which might sensitise the cells to the effects of other cytokines and/or proliferative agents. The expression of IL-7 mRNA in some nonhaematopoietic malignancies suggest the possibility for an autocrine growth pathway for IL-7.

  • The production of IL-7 by some human solid tumours including colon and other cancers suggest a possible impact on the process of tumourigenesis. Furthermore, the detection of a functional IL-7 receptor in human solid malignancies also supports this concept. While the exact effects of IL- 7 signalling activation is still unclear, the downstream signalling intermediates are upregulated in several human solid tumours including breast, lung, prostate, renal, ovarian, melanomas as well as head and neck tumours.

  • This could be explained by the possibility of the occurrence of some changes in tumour microenvironment leading to changes in tumour development, behaviour and progression. Aberrant Jak–Stat pathways could indeed result in oncogenesis in some solid tumours. Better understanding of the mechanisms underlying these aberrant pathways in IL-7 signalling may lead to the development of novel cancer therapies based on interrupting key steps in these pathways. The relationship of IL-7 and solid tumours are still far from clear.

  • Studies are currently underway to establish any relationship between IL-7 and breast cancer particularly in relation to tumour lymphangiogenesis and angiogenesis. Better understanding of the effects of IL-7 on endothelial and epithelial cell development, growth and differentiation as well as the mechanisms that control the activation of IL- 7 signalling might have an important impact on oncogenesis. Therefore more studies are required to address this important issue.

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