Unique versus redundant functions of IL-1α and IL-1β in the tumor microenvironment

Elena Voronov, Shahar Dotan, Yakov Krelin, Xiaoping Song, Moshe Elkabets, Yaron Carmi, Peleg Rider, Idan Cohen, Marianna Romzova, Irena Kaplanov, Ron N. Apte

Research output: Contribution to journalReview articlepeer-review

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-1β 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-1β and IL-1β bind to the same receptors and induce the same biological functions, but IL-1β and IL-1β differ in their compartmentalization within the producing cell or the microenvironment. IL-1β is only active in its processed, secreted form, and mediates inflammation, which promotes carcinogenesis, tumor invasiveness, and immunosuppression, whereas IL-1β 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-1β are usually low and do not stimulate broad inflammation that promotes progression. Immunosuppression induced by IL-1β in the tumor microenvironment, mainly through MDSC induction, usually inhibits or masks anti-tumor cell immunity induced by cell-associated IL-1β. However, in different tumor systems, redundant or unique patterns of IL-1β and IL-1β expression and function have been observed. 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 inflammatory diseases. Better understanding of the integrative role of IL-1β and IL-1β 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.

Original languageEnglish
Article number177
JournalFrontiers in Immunology
Volume4
Issue numberJUL
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

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

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