Paradoxical roles of IL-4 in tumor immunity

Cell Mol Immunol. 2009 Dec;6(6):415-22. doi: 10.1038/cmi.2009.53.

Abstract

Interleukin (IL)-4 is a crucial cytokine in tumor immunology. In the initial murine experiments, IL-4 exhibited potent anti-tumor ability. Tumors genetically modified to produce IL-4 were rejected, while parental tumors grew progressively. Mice rejected IL-4-producing tumors got long-lasting anti-tumor immunity. The comparative study showed that IL-4 induced the most effective immune response among several cytokines in both prophylactic and therapeutic models. All of these indicate IL-4 has strong potential as a tumor therapy agent. However, contrary evidence indeed exists, and is becoming more and more abundant which shows IL-4 is a tumor-promoting molecule. IL-4 amounts are usually elevated in human cancer patients. IL-4 knockout mice are more resistant to tumor challenge than IL-4 competent mice. Furthermore, tumor cells of various histological origins often express increased levels of IL-4 receptor in comparison to their normal counterparts. By carefully examining presently available data, we found the effects of IL-4 in tumor immunity are closely related to its sources, expressing time and dose, as well as the molecular and cellular environments. In this mini-review, we concentrate on illustrating the paradoxical roles and underlying mechanisms of IL-4 in tumor immunity and try to understand how one molecule has opposite effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Humans
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / immunology*
  • Interleukin-4 / metabolism
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Receptors, Interleukin-4 / immunology

Substances

  • Receptors, Interleukin-4
  • Interleukin-4