Cutaneous melanoma makes up only about 7% of skin cancers but is causing almost 90% of deaths. The metastatic stage is the main cause of mortality in this neoplasm and is the outcome of a complex, still poorly understood, cross-talk between tumor and other cell phenotypes. Evidence suggests Interleukin-8 (IL-8) be symbolic for advanced melanomas. 

The scientific portrait of IL-8 has been significantly changing since its discovery. Numerous IL-8 characteristics are now well-acknowledged while others still await further clarifications. Undoubtedly, IL-8 is symbolic of pathological states. It was first explored in inflammatory diseases but has now rapidly extended in tumor areas, as both pathologies are regulated by many common factors. 

In melanoma, it is agreed that IL-8 and IL-8Rs are well expressed by invasive, anti-apoptotic tumor cells. Moreover, numerous other cells from the melanoma microenvironment (MME) are managing IL-8/IL-8Rs-mediated programs which are concluded with the accumulation of immune infiltrates at tumor site, melanoma cell intravasation in vessel fluids and their extravasation and tumor noduli formation at secondary sites. The IL-8/IL-8Rs axis also operates on most immune cell phenotypes from which some have either pro- or anti-tumor activities, or both. Additionally, the stromal cell phenotypes encountered in MME gets reprogrammed by IL-8-mediated mechanisms and become intensely active in tumor fate. They supply different factors which affect both tumor cells and immune cell gallery.

IL-8/IL-8Rs axis operates similarly in all cancer types. However, the molecularity may display tumor-specific actors, which are yet to be deeply investigated. Since melanoma is an extremely heterogenic tumor, unique molecular regulators and pathways which operate in different stages and types of individuals are anticipated. Additionally, IL-8 action has to be incorporated into the general complex puzzle of CyKs which control all the paths of melanoma progression. A more genomic-wide transcriptomic analysis will suggest clarifications regarding gene clusters regulated by the IL-8/IL-8R axis in different melanoma stages and subtypes.

Source- Filimon A, Preda IA, Boloca AF, Negroiu G. Interleukin-8 in Melanoma Pathogenesis, Prognosis and Therapy-An Integrated View into Other Neoplasms and Chemokine Networks. Cells. 2021;11(1):120. Published 2021 Dec 30. doi:10.3390/cells11010120