Year: 2025
Type: article
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-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.
Source: Cancer Immunology Immunotherapy
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,590
Funders: Göran Gustafssons Stiftelser, Gyllenstiernska Krapperupsstiftelsen, Cancerfonden, Lunds Universitet, KU Leuven, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Fru Berta Kamprads Stiftelse, Science for Life Laboratory, Skånes universitetssjukhus, HudFonden, Uppsala Multidisciplinary Center for Advanced Computational Science
Awards: G1441096865, G2406212025, G2604263563, G2731258144, G3321450376, G3660823713, G4625857113, Elucidating tumor intrinsic and immune mediated factors affecting prognosis and therapy response in melanoma, G518977998, G712881263, G7198575154, The effect of tertiary lymphoid structures on cancer immunotherapy response, G796431723
OpenAlex ID: W7116990181