Checkpoint Blockade Efficacy in Uveal Melanoma Is Linked to Tumor Immunity, CD28, and CCL8

Koch E, Liguori R, Castro AA, Schliep S, Petzold A, Wessely A, Fröhlich W, Ferrazzi F, Vera J, Eckstein M, Berking C, Heppt M (2025)

Publication Type: Journal article

Publication year: 2025

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 26

Article Number: 9964

Journal Issue: 20

DOI: 10.3390/ijms26209964

Abstract

For patients with metastatic uveal melanoma (UM), tebentafusp is currently the only systemic therapy approved by the EMA and FDA, but its use is limited to HLA-A*02:01-positive individuals. Immune checkpoint blockade (ICB) represents another option, though only a small subgroup of patients benefits, and no reliable predictive biomarkers are available to date. The aim of this study was therefore to identify parameters associated with favorable ICB response. Tumor samples and clinical data from 30 patients were analyzed. Group A (n = 16) showed clinical benefit, while Group B (n = 14) experienced disease progression. NanoString® analyses revealed 258 upregulated genes in Group A, including IDO1, CD28, and CCL8. The enriched pathways were predominantly linked to immune activation, leukocyte adhesion, and responses to external stimuli. Immunohistochemistry confirmed significantly higher CD28 expression on infiltrating immune cells in Group A, while a machine learning approach identified CCL8 as a predictive marker with ~78% accuracy. Overall survival differed significantly between the groups. These findings indicate that patients responding to ICB display tumors with enhanced immune activation. CD28 and CCL8 emerged as promising candidates and should be validated in prospective studies to determine their clinical utility.

Authors with CRIS profile

Elias Koch Department of Dermatology Renato Liguori Sonderforschungsbereich/Transregio 305/1 Über die Analyse der metastatischen Koloniebildung zu neuen systemischen Krebstherapien Anne Petzold Department of Dermatology Anja Wessely Department of Dermatology Fulvia Ferrazzi Institute of Human Genetics Julio Vera González Professur für Tumorimmunologie (Schwerpunkt Systembiologie) Markus Eckstein Institute of Pathology Carola Berking Lehrstuhl für Haut- und Geschlechtskrankheiten Markus Heppt Department of Dermatology

How to cite

APA:

Koch, E., Liguori, R., Castro, A.A., Schliep, S., Petzold, A., Wessely, A.,... Heppt, M. (2025). Checkpoint Blockade Efficacy in Uveal Melanoma Is Linked to Tumor Immunity, CD28, and CCL8. International Journal of Molecular Sciences, 26(20). https://doi.org/10.3390/ijms26209964

MLA:

Koch, Elias, et al. "Checkpoint Blockade Efficacy in Uveal Melanoma Is Linked to Tumor Immunity, CD28, and CCL8." International Journal of Molecular Sciences 26.20 (2025).

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