Recent evidence indicates that targeting IL-6 provides broad therapeutic approaches to several diseases. In patients with cancer, autoimmune diseases, severe respiratory infections [e.g. coronavirus disease 2019 (COVID-19)] and wound healing, IL-6 plays a critical role in modulating the systemic and local microenvironment. Elevated serum levels of IL-6 interfere with the systemic immune response and are associated with disease progression and prognosis. As already noted, monoclonal antibodies blocking either IL-6 or binding of IL-6 to receptors have been used/tested successfully in the treatment of rheumatoid arthritis, many cancer types, and COVID-19. Therefore, in the present review, we compare the impact of IL-6 and anti-IL-6 therapy to demonstrate common (pathological) features of the studied diseases such as formation of granulation tissue with the presence of myofibroblasts and deposition of new extracellular matrix. We also discuss abnormal activation of other wound-healing-related pathways that have been implicated in autoimmune disorders, cancer or COVID-19.

• Keywords
• Cancer stroma, Granulation tissue, IL-6, Inflammation, Myofibroblast, Peripheral nerve injury, Rheumatoid arthritis, SARS-CoV-2, Wound healing,
• MeSH
• Autoimmunity MeSH
• Autoimmune Diseases * drug therapy   MeSH
• COVID-19 * MeSH
• Wound Healing MeSH
• Humans MeSH
• Tumor Microenvironment MeSH
• Neoplasms * drug therapy   MeSH
• Inflammation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The incidence of cutaneous malignant melanoma is increasing worldwide. While the treatment of initial stages of the disease is simple, the advanced disease frequently remains fatal despite novel therapeutic options . This requires identification of novel therapeutic targets in melanoma. Similarly to other types of tumours, the cancer microenvironment plays a prominent role and determines the biological properties of melanoma. Importantly, melanoma cell-produced exosomes represent an important tool of intercellular communication within this cancer ecosystem. We have focused on potential differences in the activity of exosomes produced by melanoma cells towards melanoma-associated fibroblasts and normal dermal fibroblasts. Cancer-associated fibroblasts were activated by the melanoma cell-produced exosomes significantly more than their normal counterparts, as assessed by increased transcription of genes for inflammation-supporting cytokines and chemokines, namely IL-6 or IL-8. We have observed that the response is dependent on the duration of the stimulus via exosomes and also on the quantity of exosomes. Our study demonstrates that melanoma-produced exosomes significantly stimulate the tumour-promoting proinflammatory activity of cancer-associated fibroblasts. This may represent a potential new target of oncologic therapy .

• Keywords
• Cancer-associated fibroblasts, Exosomes, IL-6, IL-8, Melanoma, Proinflammatory cytokine,
• MeSH
• Exosomes metabolism   MeSH
• Fibroblasts metabolism   pathology   MeSH
• Humans MeSH
• Melanoma, Experimental metabolism   pathology   MeSH
• Tumor Cells, Cultured MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH