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Clinical Studies

Soluble VE-cadherin as a biomarker of response to immunotherapy by anti-PD1 in metastatic melanoma

British Journal of Cancer volume 132, pages 863–865 (2025)Cite this article

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Your recently published articles [1, 2], emphasising the importance of studying cellular migration mechanisms in cancer, have retained all our attention as this can lead to the discovery of new survival markers, such as Neuroligin 4X (NLGN4X) [1] and foster the development of in vitro models for drug testing, like the pseudovascular network formation model [2]. The search for a cancer prognostic marker, particularly in melanoma, or a marker of treatment efficacy, is conducted by numerous teams [3,4,5]. Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for advanced melanoma, but only 35–45% of patients show an objective response, with a 2-year survival rate around 50% [6]. Schörghofer et al. [1] have recently identified a promising predictive factor in melanoma. They showed on a large cohort that reduced amounts of NLGN4X in the tumour—a member of the neuroligin family, whose role is to promote adhesion between cells—is a predictive marker of a metastatic melanoma phenotype. Its expression level is also inversely correlated in early stages (localised tumour) with overall survival.

We would also like to report on our experience with another molecule involved in melanoma tumour migration: VE-Cadherin. Beyond vascular mimicry, neo-angiogenesis stimulated by factors like VEGF [7] is crucial for melanoma progression. VEGF acts by triggering VE-cadherin phosphorylation, leading to the release of a soluble form, sVE [8], which serves as a biomarker in multiple cancers, including kidney cancer [9]. We hypothesised that sVE levels could serve as both a marker of tumour stage and an indicator of treatment efficacy in advanced melanoma treated with ICIs.

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Fig. 1: Soluble VE-cadherin levels in plasma from melanoma patients.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. All the data are provided in the article.

References

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Acknowledgements

We thank all patients and healthy donors, and are grateful to all the staffs in CHU, EFS (prélèvements, PLER, supports and R&D services) and CEA teams for their day-to-day support.

Funding

This work was supported by French Blood Bank and Ligue contre le Cancer Comité Isere (R19017cc-RAB 190012ccA) fundings.

Author information

Author notes

  1. These authors contributed equally: Clémentine Broche, Khémary Um.

  2. These authors jointly supervised this work: Laurence Chaperot, Julie Charles.

Authors and Affiliations

  1. Department of Dermatology, Allergology and Photobiology, Univ. Grenoble Alpes, CHU Grenoble Alpes, Grenoble, France

    Clémentine Broche, Stéphane Mouret, Marie-Thérèse Leccia, Marie Enquebecq, Aude Belbezier & Julie Charles

  2. Institute for Advanced Biosciences Team Immunobiology and Immunotherapy in Chronic Diseases, Univ. Grenoble Alpes, CNRS UMR 5309, Inserm U 1209, Grenoble, France

    Khémary Um, Marie-Thérèse Leccia, Caroline Aspord, Laurence Chaperot & Julie Charles

  3. Etablissement français du sang, Research and Development Laboratory, Grenoble, France

    Khémary Um, Caroline Aspord & Laurence Chaperot

  4. Biomicrotechnology and Functional Genomics (Biomics), Biosciences and Bioengineering for Health Laboratory, Univ. Grenoble Alpes, CNRS, InsermU 13, CEA, Institute of Interdisciplinary Research of Grenoble (IRIG), Grenoble, France

    Isabelle Vilgrain

  5. Team Cancer Targets and Experimental Therapeutics, Univ. Grenoble Alpes, CNRS UMR 5309, Inserm U 1209, Institute for Advanced Biosciences, Grenoble, France

    Stéphane Mouret, Benoit Busser & Aude Belbezier

  6. Laboratory TIMC, Univ. Grenoble Alpes, CNRS, Grenoble, France

    Arnaud Seigneurin

  7. Medical evaluation Unit, Univ. Grenoble Alpes, CHU Grenoble Alpes, Grenoble, France

    Arnaud Seigneurin

  8. Department of Internal Medicine, Univ. Grenoble Alpes, CHU Grenoble Alpes, Grenoble, France

    Laurence Bouillet

  9. Biology and Biotechnology for Health Laboratory, Univ. Grenoble Alpes, CNRS, InsermU 1292, CEA, Institute of Interdisciplinary Research of Grenoble (IRIG), Grenoble, France

    Aude Salomon

  10. Department of Clinical Biochemistry, Univ. Grenoble Alpes, CHU Grenoble Alpes, Grenoble, France

    Benoit Busser

  11. Department of Radiology, Univ. Grenoble Alpes, CHU Grenoble Alpes, Grenoble, France

    Pauline Porret

Authors
  1. Clémentine Broche
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  2. Khémary Um
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  3. Isabelle Vilgrain
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  4. Stéphane Mouret
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  5. Marie-Thérèse Leccia
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  6. Arnaud Seigneurin
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  7. Laurence Bouillet
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  8. Marie Enquebecq
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  9. Aude Salomon
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  10. Caroline Aspord
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  11. Benoit Busser
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  13. Aude Belbezier
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  14. Laurence Chaperot
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  15. Julie Charles
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Contributions

CB, KU, PP and ASa performed experiments, gathered and analysed the data, CB, BB, JC, SM and ME selected patients and collected clinical information, IV, JC and LC designed and supervised the study, LC and ASe, AB performed statistical analyses; CB, IV, AB and LC wrote original draft of the article, CA, LB and MTL helped supervising the study.

Corresponding author

Correspondence to Aude Belbezier.

Ethics declarations

Competing interests

The authors declare no competing financial interests in relation to the work described. S. Vilgrain has filed a patent related to sVE-cadherin dosage https://patents.google.com/patent/US20100120171A1/en.

Ethical approval

Reviewed and approved by local medical ethics committee.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki. All procedures were approved by the Ethics Committee of Grenoble University Hospital and declared under the reference #DC-2008-787. All participants signed informed consent forms.

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No individual person’s data in any form is included in this article.

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Broche, C., Um, K., Vilgrain, I. et al. Soluble VE-cadherin as a biomarker of response to immunotherapy by anti-PD1 in metastatic melanoma. Br J Cancer 132, 863–865 (2025). https://doi.org/10.1038/s41416-025-03026-0

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