Interferon lambda in anti-viral defense and cancer: dual roles, mechanism and therapeutic potential

The type III interferon family, known as interferon lambda (IFN-λ), consists of four isoforms (IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) and plays essential roles in immune responses. It mediates anti-viral and anti-tumoral activities and is distinguished from type I and type II interferons (IFNs) by its interaction with a unique receptor complex involving IFN-λR1 and IL-10 Rβ predominantly expressed on epithelial cells and selected immune cell populations. This interaction results in activation of the JAK-STAT signaling pathway and transcription of interferon-stimulated genes (ISGs).

IFN-λs exert anti-viral activities, particularly at epithelial and barrier surfaces, and have emerged as therapeutic agents for chronic viral infections like hepatitis C virus and influenza, providing an alternative to traditional IFN therapies with a more favorable safety profile. Beyond these anti-viral properties, IFN-λs contribute to tumor control by enhancing immune surveillance and modulating the composition of the tumor microenvironment. However, accumulating evidence indicates that IFN-λ cells may also exhibit pro-tumorigenic potential by promoting immune evasion and tumor progression in certain contexts. These opposing functions underscore the complexity of IFN-λ biology and the need for further research to elucidate the mechanisms governing its actions, identify biomarkers that predict IFN response and to develop targeted strategies that maximize its therapeutic benefits, while minimizing adverse effects.

By elucidating the complex interplay between IFN-λ and the immune system, this review provides insights into its dual functions in immune-related diseases, its potential as a biomarker for disease monitoring and prediction of therapy response, and its potential for the development of targeted therapies in cancer treatment and viral infections. However, to improve the patients' outcomes in infectious diseases and cancer management, a comprehensive understanding of its context-specific effects is required to optimize its clinical application.