Interleukin-8 in Melanoma Pathogenesis, Prognosis and Therapy-An Integrated View into Other Neoplasms and Chemokine Networks

Cutaneous melanoma accounts for only about 7% of skin cancers but is causing almost 90% of deaths. Melanoma cells have a distinct repertoire of mutations from other cancers, a high plasticity and degree of mimicry toward vascular phenotype, stemness markers, versatility in evading and suppress host immune control. They exert a significant influence on immune, endothelial and various stromal cells which form tumor microenvironment. The metastatic stage, the leading cause of mortality in this neoplasm, is the outcome of a complex, still poorly understood, cross-talk between tumor and other cell phenotypes. There is accumulating evidence that Interleukin-8 (IL-8) is emblematic for advanced melanomas. This work aimed to present an updated status of IL-8 in melanoma tumor cellular complexity, through a comprehensive analysis including data from other chemokines and neoplasms. The multiple processes and mechanisms surveyed here demonstrate that IL-8 operates following orchestrated programs within signaling webs in melanoma, stromal and vascular cells. Importantly, the yet unknown molecularity regulating IL-8 impact on cells of the immune system could be exploited to overturn tumor fate. The molecular and cellular targets of IL-8 should be brought into the attention of even more intense scientific exploration and valorization in the therapeutical management of melanoma.

Automated summary

Cutaneous melanoma, accounting for a small percentage of skin cancers but causing the majority of deaths, has unique mutations and capabilities to evade immune control. Interleukin-8 (IL-8) plays a significant role in advanced melanomas and operates in orchestrated programs within signaling webs. Understanding the molecular mechanisms of IL-8's impact on immune cells is crucial for changing the fate of tumors. Further scientific exploration of IL-8's targets in the therapeutic management of melanoma is of great importance.