Pleiotropic and differential functions of IL-1α and IL-1β shape the tumor microenvironment and affect the outcome of malignancies

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 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 languageEnglish
Title of host publicationThe Tumor Immunoenvironment
PublisherSpringer Netherlands
Pages197-222
Number of pages26
Volume9789400762176
ISBN (Electronic)9789400762176
ISBN (Print)940076216X, 9789400762169
DOIs
StatePublished - 1 Jan 2013

Keywords

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

ASJC Scopus subject areas

  • Medicine (all)

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