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Immunohistochemical characterisation of the immune landscape in primary uveal melanoma and liver metastases

British Journal of Cancer volume 129, pages 772–781 (2023) Cite this article

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Abstract

Background

The immune landscape of uveal melanoma liver metastases (UMLM) has not been sufficiently studied.

Methods

Immune cell infiltrates (ICIs), PD-1 and PD-L1 were characterised in 62 UMLM and 28 primary uveal melanomas (PUM). ICI, PD-1 and PD-L1 were scored as: (1) % tumoral area occupied by tumour-infiltrating lymphocytes or macrophages (TILs, TIMs) and (2) % perTumoral (perT) area. ICIs and other variables including histopathologic growth patterns (HGPs), replacement and desmoplastic, of UMLM were analysed for their prognostic value.

Results

ICIs recognised by haematoxylin-eosin-saffron (HES) and IHC (e.g., T cells (CD3), B cells (CD20). Macrophages (CD68), (CD163), were primarily localised to the perT region in PUM and UMLM and were more conspicuous in UMLM. HES, CD3, CD4, FoxP3, CD8, CD20, PD-1 TILs were scant (<5%). TIMs were more frequent, particularly in UMLM than in PUM. Both CD68+ TIMs and HGPs remained significant on multivariate analysis, influencing overall (OS) and metastasis-specific overall survival (MSOS). CD68 + , CD163+ and CD20+ perT infiltrates in UMLM predicted increased OS and MSOS on univariate analysis.

Conclusions

TILs and PD-L1 have no predictive value in PUM or UMLM. CD68+ and CD163+TIMs, CD20+ perT lymphocytes, and HGPs are important prognostic factors in UMLMs.

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Fig. 1: Boxplots showing significant differences in immune staining scores between paired primary tumours (PT) and liver metastases (LM) of uveal melanoma.
The alternative text for this image may have been generated using AI.
Fig. 2: Boxplots showing significant differences in immune staining scores between all primary tumours (PT) and liver metastases (LM) of uveal melanoma.
The alternative text for this image may have been generated using AI.
Fig. 3: Immunohistochemistry showing expression of lymphocyte markers in primary uveal melanoma and uveal melanoma liver metastases.
The alternative text for this image may have been generated using AI.
Fig. 4: Immunohistochemistry showing expression of macrophage markers in uveal melanoma liver metastases.
The alternative text for this image may have been generated using AI.
Fig. 5: Boxplots showing significant differences for immune cell infiltrates in uveal melanoma liver metastases analysed for various prognostic factors.
The alternative text for this image may have been generated using AI.
Fig. 6: Uveal melanoma liver metastases and CD68 tumour-infiltrating macrophages (TIMs).
The alternative text for this image may have been generated using AI.

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Data availability

All data are available upon request in writing from the corresponding author Raymond Barnhill.

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Funding

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 667787.

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Authors and Affiliations

  1. Department of Surgery, Institut Curie, Paris, France

    Pascale Mariani

  2. Department of Medical Oncology, Institut Curie, Paris, France

    Nouritza Torossian, Manuel Rodrigues, Emanuela Romano & Sophie Piperno-Neumann

  3. Faculty of Medicine and Health Sciences, University of Antwerp–MIPRO Center for Oncological Research (CORE) - TCRU, GZA Sint-Augustinus, Antwerp, Belgium

    Steven van Laere & Peter Vermeulen

  4. Department of Translational Research, Institut Curie, Paris, France

    Leanne de Koning, Sergio Roman-Roman, Claire Lugassy & Raymond Barnhill

  5. Laboratoire d’immunologie clinique, Institut Curie, Paris, France

    Olivier Lantz

  6. Centre d’investigation Clinique en Biothérapie, Institut Curie (CIC-BT1428), Paris, France

    Olivier Lantz

  7. INSERM U932, PSL University, Institut Curie, Paris, France

    Olivier Lantz

  8. Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée Par la Ligue Nationale Contre le Cancer, Institut Curie, Paris, France

    Manuel Rodrigues & Marc-Henri Stern

  9. Department of Pathology, Institut Curie, Paris, France

    Sophie Gardrat, Laetitia Lesage, Gabriel Champenois & André Nicolas

  10. Department of Ophthalmology, Institut Curie, Paris, France

    Alexandre Matet & Nathalie Cassoux

  11. Université de Paris Cité UFR de Médecine, Paris, France

    Alexandre Matet, Nathalie Cassoux & Raymond Barnhill

  12. Department of Radiology, Institut Curie, Paris, France

    Vincent Servois

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Contributions

RB confirms that he had full access to the data in the study and final responsibility for the decision to submit for publication. RB wrote the manuscript with the assistance of NT, SVL and LK. RB developed the methodology. RB collected and analysed data. SVL performed statistical analyses and analysed data. LL, GC and AN performed immunohistochemistry, scanned glass slides, and managed glass microslides. PM and SPN collected data. All the authors reviewed and approved the manuscript.

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Correspondence to Raymond Barnhill.

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The study was approved by the Ethics Committee, Institut Curie. All patients agreed to participate in the study based on informed consent. The study was performed in accordance with the Declaration of Helsinki.

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Mariani, P., Torossian, N., van Laere, S. et al. Immunohistochemical characterisation of the immune landscape in primary uveal melanoma and liver metastases. Br J Cancer 129, 772–781 (2023). https://doi.org/10.1038/s41416-023-02331-w

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