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Neoadjuvant immune checkpoint inhibition improves protection against hepatic melanoma metastasis

Background - Liver metastasis of cutaneous melanoma (CM) correlates with a decreased response to immune checkpoint inhibition (ICI). Here, we investigated whether neoadjuvant ICI protects against liver metastasis to prevent the development of therapy resistances. - Methods - A stage II CM was modele...

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Main Authors: Wohlfeil, Sebastian A. (Author) , Weller, Céline (Author) , Dietsch, Bianca (Author) , Agardy, Dennis (Author) , Boschert, Tamara (Author) , Vormehr, Sheila Ann (Author) , Dormann, Christof (Author) , Straub, Niklas (Author) , Häfele, Verena (Author) , Platten, Michael (Author) , Goerdt, Sergij (Author) , Géraud, Cyrill (Author)
Format: Article (Journal)
Language:English
Published: 1 November 2025
In: Cancer letters
Year: 2025, Volume: 632, Pages: 1-12
ISSN:1872-7980
DOI:10.1016/j.canlet.2025.217950
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.canlet.2025.217950
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0304383525005191
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Author Notes:Sebastian A. Wohlfeil, Céline Weller, Bianca Dietsch, Dennis Alexander Agardy, Tamara Boschert, Sheila A. Vormehr, Christof Dormann, Niklas Straub, Verena Häfele, Michael Platten, Sergij Goerdt, Cyrill Géraud
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Summary:Background - Liver metastasis of cutaneous melanoma (CM) correlates with a decreased response to immune checkpoint inhibition (ICI). Here, we investigated whether neoadjuvant ICI protects against liver metastasis to prevent the development of therapy resistances. - Methods - A stage II CM was modeled by intracutaneous injections of WT31 or B16F10 luc2 melanoma cells. Combined ICI (anti-PD-1/anti-CTLA-4) was applied in murine models of hepatic melanoma metastasis comparing neoadjuvant or adjuvant regimens. Immune cell composition and responses in the liver and CMs were comparatively analyzed by scRNA-Seq, flow cytometry, immunofluorescence, in situ hybridization and multiplex cytokine assays. - Results - Neoadjuvant ICI resulted in improved protection against liver metastasis in comparison to adjuvant therapy. This superior response was associated with an expansion of T cells in CMs, the peripheral blood and the liver. An increased expression of TH1-associated markers and a downregulation of TH2-associated markers were detected in T cells from CMs and livers of mice by scRNA-Seq and immunofluorescence after neoadjuvant ICI. Analysis of hepatic cytokines also revealed lower levels of TH2-associated IL-4 and of IL-15. - Conclusion - Our data demonstrate that neoadjuvant ICI provides superior protection against hepatic melanoma metastasis with a shift towards an anti-tumor TH1 immune response. Therefore, neoadjuvant ICI is a promising therapeutic option for CM to prevent the development of organ-specific therapy resistance mechanisms.
Item Description:Online verfügbar: 24 Juli 2025, Artikelversion: 15. August 2025
Gesehen am 17.11.2025
Physical Description:Online Resource
ISSN:1872-7980
DOI:10.1016/j.canlet.2025.217950

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