EVasion · Evasion of antitumor immunity and immunotherapy by melanoma extracellular vesicles

Evasion of antitumor immunity and immunotherapy by melanoma extracellular vesicles

Melanoma is the deadliest form of skin cancer. In 2022, around 331,722 people were diagnosed with melanoma, and approximately 58,667 died from the disease. When detected early, melanoma is highly treatable, with a 5-year relative survival rate exceeding 99%. However, if it spreads to distant parts of the body (known as metastatic melanoma), the prognosis worsens significantly. In such cases, the 5-year relative survival rate drops to about 35%, meaning that only 35% of patients with advanced melanoma are expected to live for at least five years after diagnosis. Immunotherapy, which helps the immune system fight diseases, has shown promising results in treating metastatic melanoma. Immune checkpoint inhibitors (ICI) are a type of immunotherapy that is currently used for the treatment of advanced melanoma. However, only around 50% of patients respond to ICI treatment. To improve outcomes, it is critical to understand why some patients respond to these therapies while others do not. Extracellular vesicles (EVs) are very small particles released by all cells. They carry and transfer biomolecules (e.g. proteins, lipids, nucleic acids, and metabolites) throughout the body. In recent years, EVs have been shown to also act as protein decoys, by binding and sequestering soluble proteins, preventing them from interacting with their intended targets. Previous research from our group found that EVs released by melanoma cells carry receptors for interferon-gamma (IFNγ). IFNγ plays a pivotal role in the body’s immune response to cancer, leading to tumor cell killing and to activation of immune cells. Importantly, defects in the IFNγ signaling pathway have been linked to resistance to ICI therapy. Since EVs derived from tumor cells are known to promote tumor growth and metastases, we hypothesized that they modulate the bioavailability and activity of IFNγ, contributing to tumor development, metastases formation, and resistance to ICI therapy. Our research has the potential to unveil a novel cancer immune evasion mechanism mediated by EVs. Understanding the mechanisms behind antitumor resistance is essential for developing alternative or complementary treatment strategies to improve response to ICIs and other cancer therapies. This work could also help identify biomarkers that predict how patients will respond to treatment, paving the way for more personalized and effective cancer therapies. Importantly, our findings may also apply to other types of cancer beyond melanoma.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз