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<p>Immune checkpoint blockade (ICB) therapy can restore T cell function in tumors, but not all patients benefit, and the mechanisms behind this remain unclear. In this study, we used patient-derived organotypic (PDO) cultures from metastatic melanoma to examine transcriptomic and cellular changes following ex vivo T cell stimulation. Genomic and transcriptomic features were preserved during PDO formation, capturing melanoma heterogeneity. PDOs from ICB-responsive patients showed rapid T cell expansion upon T cell stimulation, unlike those from ICB-resistant tissue. Resistant tissue harbored T cells lacking activation and checkpoint markers, suggesting non-tumor-reactive T cells. A T cell-specific transcriptomic score, activated in responsive PDOs, correlated with improved overall and relapse-free survival in metastatic melanoma patients treated with ICB. These findings demonstrate that ex vivo analysis is a viable tool to investigate mechanisms of ICB response and may help identify predictive biomarkers for patient outcome.</p>

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Modeling anti-tumor immune responses using patient-derived melanoma organoids

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月23日

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  • Kamila Kaminska,
  • Bengt Phung,
  • Jacob Karlström,
  • Martin Lauss,
  • Katja Harbst,
  • Teresa Svensson,
  • Kristian Pietras,
  • Kari Nielsen,
  • Ana Carneiro,
  • Henrik Ekedahl,
  • Karolin Isaksson,
  • Göran Jönsson

摘要

Immune checkpoint blockade (ICB) therapy can restore T cell function in tumors, but not all patients benefit, and the mechanisms behind this remain unclear. In this study, we used patient-derived organotypic (PDO) cultures from metastatic melanoma to examine transcriptomic and cellular changes following ex vivo T cell stimulation. Genomic and transcriptomic features were preserved during PDO formation, capturing melanoma heterogeneity. PDOs from ICB-responsive patients showed rapid T cell expansion upon T cell stimulation, unlike those from ICB-resistant tissue. Resistant tissue harbored T cells lacking activation and checkpoint markers, suggesting non-tumor-reactive T cells. A T cell-specific transcriptomic score, activated in responsive PDOs, correlated with improved overall and relapse-free survival in metastatic melanoma patients treated with ICB. These findings demonstrate that ex vivo analysis is a viable tool to investigate mechanisms of ICB response and may help identify predictive biomarkers for patient outcome.