TY  - JOUR
AU  - Wohlfeil, Sebastian
AU  - Weller, Céline
AU  - Dietsch, Bianca
AU  - Agardy, Dennis Alexander
AU  - Boschert, Tamara
AU  - Vormehr, Sheila A
AU  - Dormann, Christof
AU  - Straub, Niklas
AU  - Häfele, Verena
AU  - Platten, Michael
AU  - Goerdt, Sergij
AU  - Géraud, Cyrill
TI  - Neoadjuvant immune checkpoint inhibition improves protection against hepatic melanoma metastasis.
JO  - Cancer letters
VL  - 632
SN  - 0304-3835
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DKFZ-2025-01554
SP  - 217950
PY  - 2025
N1  - #EA:A370# / Volume 632, 1 November 2025, 217950
AB  - 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.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.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.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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40714065
DO  - DOI:10.1016/j.canlet.2025.217950
UR  - https://inrepo02.dkfz.de/record/303203
ER  -