The insulin-like growth factor-binding protein (IGFBP) family modulates the tumor immune microenvironment through both IGF-dependent and IGF-independent pathways, presenting a promising target for novel cancer immunotherapies.
Abstract Background The insulin-like growth factor-binding protein (IGFBP) family consists of soluble bioactive molecules that, together with insulin-like growth factors (IGFs) and their receptors, are critical modulators of endocrine, metabolic, and immune functions. IGFBPs serve as signaling intermediaries in fundamental cellular processes such as migration, differentiation, proliferation, and apoptosis. Although their role in immune regulation is well-documented, this understanding has not yet led to significant clinical progress, particularly in research utilizing human specimens. Main body This review synthesizes current knowledge on the functions and mechanisms of IGFBPs within immune regulation and tumor immunology, highlighting their therapeutic potential. We specifically examine how IGFBPs influence diverse cell populations residing in the tumor immune microenvironment, primarily through IGF-dependent and IGF-independent pathways. The article highlights future research directions and potential targets for novel immunotherapy strategies. This article also synthesizes the latest clinical research data on the correlation between IGFBP expression levels and patient prognosis across various cancer types, strengthening the translational potential of IGFBPs as targets for immunotherapy. Conclusion By detailing the impact of IGFBPs on the tumor immune landscape, we position this protein family as promising targets for the development of novel cancer immunotherapies.
Lei et al. (2026) conducted a review in Cancer. IGFBP-targeted immunotherapy was evaluated. The insulin-like growth factor-binding protein (IGFBP) family modulates the tumor immune microenvironment through both IGF-dependent and IGF-independent pathways, presenting a promising target for novel cancer immunotherapies.