Abstract
Interleukin-1 (IL-1) is a major alarm upstream pro-inflammatory cytokine that also affects immunity and hemopoiesis 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 and also in the activation of anti-tumor immunity. IL-1α and IL-1β are the major agonists of IL-1, while IL-1Ra is a physiological inhibitor of pre-formed IL-1. In their secreted form, IL-1α and IL-1β bind to the same receptors and induce the same biological functions. However, IL-1α and IL-1β differ in their compartmentalization within the producing cell or the microenvironment. IL-1β is only active in its secreted form and mediates inflammation, which promotes carcinogenesis, tumor invasiveness and immunosuppression. On the other hand, IL-1α is mainly cell-associated; in the context of tumors, host- and tumor cell-derived IL-1α stimulates anti-tumor immunity, rather than inflammation. Recent breakthroughs in inflammasome biology and IL-1β processing/secretion have spurred the development of novel anti-IL-1 agents which are being used in clinical trials in patients with diverse diseases with inflammatory manifestations. Better understanding of the integrative role of IL-1α and IL-1β in the malignant process will enable 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.
Original language | English |
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Title of host publication | The Tumor Immunoenvironment |
Publisher | Springer Netherlands |
Pages | 197-222 |
Number of pages | 26 |
ISBN (Electronic) | 9789400762176 |
ISBN (Print) | 940076216X, 9789400762169 |
DOIs | |
State | Published - 1 Jan 2013 |
Keywords
- Anti-tumor immunity
- Carcinogenesis
- IL-1
- IL-1Ra
- Immunogenicity
- Immunotherapy
- Tumor invasiveness
- Tumor-host interactions
ASJC Scopus subject areas
- General Medicine