Advancements in understanding and treating CXCL16/CXCR6 in tumors and in inflammatory diseases: a narrative review.

The CXCL16/CXCR6 axis exerts a multifaceted, bidirectional regulatory influence across various pathological processes, including neoplasms and inflammatory disorders. Its functions are notably context-dependent, possessing the capacity to both inhibit and facilitate disease progression. This article aims to systematically analyze this 'double-edged sword' characteristic by providing an exhaustive review of the axis's functional spectrum across different diseases. Initially, we explore its bidirectional regulatory mechanisms within the tumor microenvironment, emphasizing the influence of tumor heterogeneity and the distinct roles of CXCL16 isoforms (membrane-bound and soluble) in determining functional outcomes. Subsequently, we broaden the discussion to encompass inflammatory diseases, examining the axis's potential as a predictive marker in these conditions and presenting the latest insights into its role in diseases such as asthma. Additionally, we provide a review of current advancements in drug development targeting this axis and elucidate its mechanisms of action. Ultimately, the paper underscores that accurately identifying the critical nodes where the CXCL16/CXCR6 axis alters its function is the central challenge and opportunity for the development of targeted therapies.