Background: Melanoma is the most aggressive skin cancer, with a 50% five-year mortality in metastatic or unresectable cases. Non-invasive biomarkers are crucial for guiding treatment. MicroRNAs (miRNAs), especially those encapsulated in extracellular vesicles (EVs), are stable in plasma and hold promise as biomarkers. Methods: This study analyzed EV-associated miRNAs (EV-miRNAs) from 50 blood samples of 18 stage III-IV melanoma patients treated with anti-CTLA-4 immunotherapy and a DNA hypomethylating agent. Samples were collected at baseline, week 4, and week 12. Patients were classified as responders (R) or non-responders (NR). Results: A baseline signature of four EV-miRNAs predicted primary resistance. Treatment altered 15 EV-miRNAs at week 4 and 51 at week 12; nine were consistently modulated. At week 12, 27 EV-miRNAs differed between NR and R, with miR-1203 and miR-566-3p up-regulated in NR, linked to resistance and poor survival. Conclusions: These results highlight EV-miRNAs as non-invasive biomarkers for predicting and monitoring therapy response.
Circulating EV-microRNAs are dynamic biomarkers of resistance to therapeutic immunomodulation in metastatic melanoma / Splendiani, E., Besharat, Z.M., Sabato, C., Noviello, T.M.R., Lofiego, M.F., D'Alonzo, V., Valente, M., Solmonese, L., Covre, A., Coral, S., Caruso, F.P., Autilio, T.M., Simeone, I., Po, A., Citarella, A., Catanzaro, G., Mortarini, R., Anichini, A., Maio, M., Ceccarelli, M., et al.. - In: COMMUNICATIONS MEDICINE. - ISSN 2730-664X. - 6:1(2026). [10.1038/s43856-026-01629-z]
Circulating EV-microRNAs are dynamic biomarkers of resistance to therapeutic immunomodulation in metastatic melanoma
Splendiani, Elena;Besharat, Zein Mersini;Autilio, Tanja Milena;Po, Agnese;Ferretti, Elisabetta
2026
Abstract
Background: Melanoma is the most aggressive skin cancer, with a 50% five-year mortality in metastatic or unresectable cases. Non-invasive biomarkers are crucial for guiding treatment. MicroRNAs (miRNAs), especially those encapsulated in extracellular vesicles (EVs), are stable in plasma and hold promise as biomarkers. Methods: This study analyzed EV-associated miRNAs (EV-miRNAs) from 50 blood samples of 18 stage III-IV melanoma patients treated with anti-CTLA-4 immunotherapy and a DNA hypomethylating agent. Samples were collected at baseline, week 4, and week 12. Patients were classified as responders (R) or non-responders (NR). Results: A baseline signature of four EV-miRNAs predicted primary resistance. Treatment altered 15 EV-miRNAs at week 4 and 51 at week 12; nine were consistently modulated. At week 12, 27 EV-miRNAs differed between NR and R, with miR-1203 and miR-566-3p up-regulated in NR, linked to resistance and poor survival. Conclusions: These results highlight EV-miRNAs as non-invasive biomarkers for predicting and monitoring therapy response.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
