Dichotomy of IL-27 in tumor immunity.

IL-27, a cytokine with pleiotropic immunomodulatory functions, has garnered increasing attention in the context of tumor immunity, and its role in the tumor microenvironment (TME) is complex and just beginning to unravel. IL-27 is pivotal in polarizing immune responses toward an antitumor phenotype, promoting T-cell differentiation, enhancing cytotoxicity, and reducing the number of immunosuppressive elements within the tumor microenvironment. It also directly affects cancer cells, inducing apoptosis and inhibiting angiogenesis. However, IL-27 is a double-edged sword that can also promote mechanisms of action, inducing the expression of inhibitory molecules such as PD-L1 or IL-10 and inhibiting the maturation of dendritic cells. Here, we recapitulate the intricate mechanisms of IL-27, providing a comprehensive understanding of its immune-stimulating and immune-suppressing functions in the TME. This challenge is crucial for designing immunotherapies based on IL-27 in cancer.