IGFBP-6: At the Crossroads of Immunity, Tissue Repair and Fibrosis

Insulin-like growth factors binding protein-6 (IGFBP-6) is involved in a relevant number of cellular activities and represents an important factor in the immune response, particularly in human dendritic cells (DCs). Over the past several years, significant insights into the IGF-independent effects of IGFBP-6 were discovered, such as the induction of chemotaxis, capacity to increase oxidative burst and neutrophils degranulation, ability to induce metabolic changes in DCs, and, more recently, the regulation of the Sonic Hedgehog (SHH) signaling pathway during fibrosis. IGFBP-6 has been implicated in different human diseases, and it plays a rather controversial role in the biology of tumors. Notably, well established relationships between immunity, stroma activity, and fibrosis are prognostic and predictive of response to cancer immunotherapy. This review aims at describing the current understanding of mechanisms that link IGFBP-6 and fibrosis development and at highlighting the multiple roles of IGFBP-6 to provide an insight into evolutionarily conserved mechanisms that can be relevant for inflammation, tumor immunity, and immunological diseases.