Role of IL-34 in Tumors and Its Application to Regulate Inflammation

Interleukin (IL)-34 is a relatively recently discovered cytokine which binds to colony-stimulating factor-1 receptor (CSF-1R). So far, there has been no clear explanation as to why CSF-1R requires two ligands. While CSF-1 is ubiquitously expressed, the expression of IL-34 is relatively restricted. However, it has been revealed that IL-34 expression increases in various diseases and is associated with their pathology. Naturally, both IL-34 and CSF-1 stimulate CSF-1R, thereby contributing to the differentiation of monocytes into macrophages. In many cases, the induced macrophages significantly influence the disease pathology. In particular, we have demonstrated that IL-34 expression in cancer is deeply involved in tumor progression and therapeutic resistance. We have shown that the blockade of IL-34 significantly improved therapeutic efficacy such as chemotherapy, radiotherapy, and immune checkpoint blockade against IL-34-expressing cancers. Recently, since macrophages induced by IL-34 exhibit immunosuppressive properties, whereas IL-34 can enhance inflammation, there is growing interest in actively regulating inflammation utilizing IL-34. In this review article, we provide an overview of the characteristics and roles of IL-34 and discuss how it could be applied to future diagnostics and therapeutics.