Paradoxical roles of IL-4 in tumor immunity.
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.
Li
Zhiguang
Z
National Laboratory of Biomacromolecules, China-Japan Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Chen
Lin
L
Qin
Zhihai
Z
D000818:Animals; D018450:Disease Progression; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D019948:Receptors, Interleukin-4 / Q000276:immunology
D019948:Receptors, Interleukin-4; D015847:Interleukin-4