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Background <p>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.</p> Methods <p>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).</p> Results <p>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.</p> Conclusions <p>These results highlight EV-miRNAs as non-invasive biomarkers for predicting and monitoring therapy response.</p>

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Circulating EV-microRNAs are dynamic biomarkers of resistance to therapeutic immunomodulation in metastatic melanoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月8日

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  • Elena Splendiani,
  • Zein Mersini Besharat,
  • Claudia Sabato,
  • Teresa Maria Rosaria Noviello,
  • Maria Fortunata Lofiego,
  • Vincenzo D’Alonzo,
  • Monica Valente,
  • Laura Solmonese,
  • Alessia Covre,
  • Sandra Coral,
  • Francesca Pia Caruso,
  • Tanja Milena Autilio,
  • Ines Simeone,
  • Agnese Po,
  • Anna Citarella,
  • Giuseppina Catanzaro,
  • Roberta Mortarini,
  • Andrea Anichini,
  • Michele Maio,
  • Michele Ceccarelli,
  • Anna Maria Di Giacomo,
  • Elisabetta Ferretti

摘要

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.