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

Kaminska, Kamila LU ; Phung, Bengt LU ; Karlström, Jacob LU ; Lauss, Martin LU ; Harbst, Katja LU orcid ; Svensson, Teresa LU ; Pietras, Kristian LU orcid ; Nielsen, Kari LU orcid ; Carneiro, Ana LU orcid and Ekedahl, Henrik LU , et al. (2026) In Cancer Immunology, Immunotherapy 75(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer, Immune response, Melanoma, Patient-derived organoid, PD1
in
Cancer Immunology, Immunotherapy
volume
75
issue
1
article number
24
publisher
Springer
external identifiers
  • pmid:41432764
  • scopus:105025600751
ISSN
0340-7004
DOI
10.1007/s00262-025-04269-9
project
BioMEL
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
56173753-ef8c-4cbe-a983-d587d48a445f
date added to LUP
2026-01-09 10:07:22
date last changed
2026-01-10 03:11:44
@article{56173753-ef8c-4cbe-a983-d587d48a445f,
  abstract     = {{<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>}},
  author       = {{Kaminska, Kamila and Phung, Bengt and Karlström, Jacob and Lauss, Martin and Harbst, Katja and Svensson, Teresa and Pietras, Kristian and Nielsen, Kari and Carneiro, Ana and Ekedahl, Henrik and Isaksson, Karolin and Jönsson, Göran}},
  issn         = {{0340-7004}},
  keywords     = {{Cancer; Immune response; Melanoma; Patient-derived organoid; PD1}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer}},
  series       = {{Cancer Immunology, Immunotherapy}},
  title        = {{Modeling anti-tumor immune responses using patient-derived melanoma organoids}},
  url          = {{http://dx.doi.org/10.1007/s00262-025-04269-9}},
  doi          = {{10.1007/s00262-025-04269-9}},
  volume       = {{75}},
  year         = {{2026}},
}