Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

Int J Mol Sci. 2020 Aug 20;21(17):6009. doi: 10.3390/ijms21176009.

Abstract

IL-1 belongs to a family of 11 members and is one of the seven receptor-agonists with pro-inflammatory activity. Beyond its biological role as a regulator of the innate immune response, IL-1 is involved in stress and chronic inflammation, therefore it is responsible for several pathological conditions. In particular, IL-1 is known to exert a critical function in malignancies, influencing the tumor microenvironment and promoting cancer initiation and progression. Thus, it orchestrates immunosuppression recruiting pro-tumor immune cells of myeloid origin. Furthermore, new recent findings showed that this cytokine can be directly produced by tumor cells in a positive feedback loop and contributes to the failure of targeted therapy. Activation of anti-apoptotic signaling pathways and senescence are some of the mechanisms recently proposed, but the role of IL-1 in tumor cells refractory to standard therapies needs to be further investigated.

Keywords: IL-1; cancer; resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • Immune Tolerance / immunology
  • Interleukin-1alpha / physiology*
  • Interleukin-1beta / physiology*
  • Ligands
  • Molecular Targeted Therapy
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / metabolism*
  • Tumor Microenvironment

Substances

  • IL1A protein, human
  • IL1B protein, human
  • Interleukin-1alpha
  • Interleukin-1beta
  • Ligands
  • Receptors, Interleukin-1