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

ABSTRACT: 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-

SUBMITTER: Kaminska K 

PROVIDER: S-EPMC12728156 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature