Unique Versus Redundant Functions of IL-1? and IL-1? in the Tumor Microenvironment.

ABSTRACT: Interleukin-1 (IL-1) is a major "alarm" upstream pro-inflammatory cytokine that also affects immunity and hematopoiesis by inducing cytokine cascades. In the tumor arena, IL-1 is produced by malignant or microenvironmental cells. As a pleiotropic cytokine, IL-1 is involved in tumorigenesis and tumor invasiveness but also in the control of anti-tumor immunity. IL-1? and IL-1? are the major agonists of IL-1, while IL-1Ra is a physiological inhibitor of pre-formed IL-1. In their secreted form, IL-1? and IL-1? bind to the same receptors and induce the same biological functions, but IL-1? and IL-1? differ in their compartmentalization within the producing cell or the microenvironment. IL-1? is only active in its processed, secreted form, and mediates inflammation, which promotes carcinogenesis, tumor invasiveness, and immunosuppression, whereas IL-1? is mainly cell-associated and in the tumor context, when expressed on the cell membrane, it stimulates anti-tumor cell immunity manifested by tumor regression. In the tumor milieu, extracellular levels of IL-1? are usually low and do not stimulate broad inflammation that promotes progression. Immunosuppression induced by IL-1? in the tumor microenvironment, mainly through MDSC induction, usually inhibits or masks anti-tumor cell immunity induced by cell-associated IL-1?. However, in different tumor systems, redundant or unique patterns of IL-1? and IL-1? expression and function have been observed. Recent breakthroughs in inflammasome biology and IL-1? processing/secretion have spurred the development of novel anti-IL-1 agents, which are being used in clinical trials in patients with diverse inflammatory diseases. Better understanding of the integrative role of IL-1? and IL-1? in distinct malignancies will facilitate the application of novel IL-1 modulation approaches at the bedside, in cancer patients with minimal residual disease (MRD), as an adjunct to conventional approaches to reduce the tumor burden.

SUBMITTER: Voronov E 

PROVIDER: S-EPMC3703603 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature