IL-1 is a major cytokine that controls the balance between inflammation and immunity in the tumor microenvironment

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

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, but also in the activation of anti-tumor immunity. In the tumor milieu, IL-1 represents a feasible candidate cytokine for modulation, in order to tilt the balance between inflammation and immunity towards favorable induction of anti-tumor responses. 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 antitumor 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. IL-1Ra is already FDA-approved and has been shown to be safe and efficient in alleviating symptoms of rheumatoid arthritis. In experimental cancer, IL-1Ra attenuates tumor-mediated inflammation and invasiveness. 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 languageEnglish
Title of host publicationThe Inflammatory Milieu of Tumors
Subtitle of host publicationCytokines and Chemokines that Affect Tumor Growth and Metastasis
PublisherBentham Science Publishers Ltd.
Pages57-80
Number of pages24
ISBN (Print)9781608055203
DOIs
StatePublished - 1 Dec 2012

Keywords

  • Anti-tumor immunity
  • Carcinogenesis
  • IL-1
  • Immunogenicity
  • Immunotherapy
  • Tumor invasiveness
  • Tumor-host interactions

ASJC Scopus subject areas

  • Medicine (all)

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