Peer-Reviewed Publication
Med Image Anal2026;115104334.September 17, 2026Journal Article
Associations between spatial distribution of immune cell subsets and clinical outcomes in patients with advanced melanoma treated with immune checkpoint inhibitors: results from the PUMA challenge.
Mark Schuiveling1, Hong Liu2, Daniel Eek2, Martina Hanusová2, Isabella A J van Duin3, Laurens S Ter Maat4, Janneke C van der Weerd5, Franchette van den Berkmortel6, Christian U Blank7, Gerben E Breimer8, Femke H Burgers7, Marye Boers-Sonderen9, Alfons J M van den Eertwegh10, Jan Willem B de Groot11, John B A G Haanen12, Geke A P Hospers13, Ellen Kapiteijn14, Djura Piersma15, Lieke Simkens16, Hans M Westgeest17, Anne M R Schrader18, Paul J van Diest8, Jiaqi Lv19, Yijie Zhu19, Carmen Guadalupe Colin Tenorio20, Brinder Singh Chohan21, Mark Eastwood19, Shan E Ahmed Raza19, Nima Torbati22, Anastasia Meshcheryakova23, Diana Mechtcheriakova23, Amirreza Mahbod22, Daniel Adams24, Adrian Galdran25, Josien P W Pluim2, Willeke A M Blokx8, Karijn P M Suijkerbuijk3, Mitko Veta2
1Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CG, the Netherlands. Electronic address: m.schuiveling@umcutrecht.nl.
2Medical Image Analysis, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, Eindhoven, , 5600 MB, the Netherlands.
3Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CG, the Netherlands.
4Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CG, the Netherlands.
5Department of Pathology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, 9713 GZ, the Netherlands.
6Department of Medical Oncology, Zuyderland Medical Center Sittard, Dr. H. van der Hoffplein 1, Sittard-Geleen, 6162 BG, the Netherlands.
7Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, the Netherlands.
8Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CG, the Netherlands.
9Department of Medical Oncology, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen, 6525 GA, the Netherlands.
10Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, Amsterdam, 1081 HZ, the Netherlands.
11Isala Oncology Center, Isala, Dokter van Heesweg 2, Zwolle, 8025 AB, the Netherlands.
12Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, the Netherlands; Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333ZA, the Netherlands; Division of Molecular Oncology and Immunology, Oncode Institute, Amsterdam, 1066 CX, the Netherlands; Melanoma Clinic, Center Hospitalier Universitaire Vaudois, Lausanne, 1005, Switzerland.
13Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, 9713 GZ, the Netherlands.
14Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333ZA, the Netherlands.
15Department of Internal Medicine, Medisch Spectrum Twente, Koningsplein 1, Enschede, 7512 KZ, the Netherlands.
16Department of Internal Medicine, Maxima Medical Center, De Run 4600, Eindhoven, 5504 DB, the Netherlands.
17Department of Internal Medicine, Amphia Hospital, Molengracht 21, Breda, 4818 CK, the Netherlands.
18Department of Pathology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, the Netherlands.
19Tissue Image Analytics Centre, Department of Computer Science, University of Warwick, Coventry, United Kingdom.
20Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria; TissueGnostics GmbH, United Kingdom.
21University Hospitals of Derby and Burton NHS Foundation Trust, United Kingdom.
22Research Center for Medical Image Analysis and Artificial Intelligence, Department of Medicine, Faculty of Medicine and Dentistry, Danube Private University, Krems an der Donau, 3500, Austria.
23Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, 1090, Austria; Comprehensive Center for AI in Medicine (CAIM), Medical University of Vienna, Vienna, 1090, Austria.
24The Cancer Epidemiology and Prevention Research Unit, The Institute of Cancer Research, London and Imperial College London, London, UK; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
25Laboratoire d'imagerie, de vision et d'intelligence artificielle (LIVIA), ETS, Montréal, Canada.
Abstract
Patients with advanced melanoma are treated with immune checkpoint inhibitors (ICIs), yet <50% of patients achieve a durable response while all patients are exposed to the risk of severe side effects. Tumor-infiltrating lymphocytes (TILs) in pathology images are associated with ICI outcomes, but manual assessment is subjective. In addition, the predictive value of other immune cell subsets, includ…
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