Mechanism and modulation of organ-specific therapy responses in metastatic melanoma (08)

• Subject Area: Immunology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318346496

This study explores how tumor-intrinsic signaling, particularly IκBζ expression, drives organ-specific immunotherapy resistance in melanoma. We found that IκBζ, a co-factor of NF-κB, promotes resistance by excluding cytotoxic immune cells from the tumor microenvironment (TME). We hypothesize that the liver TME, especially macrophages/Kupffer cells and plate-lets, induces IκBζ in melanoma cells—unlike in lung metastases. The project aims to validate this by examining IκBζ’s role in liver vs. lung metastasis formation and its interaction with the TME. We will test whether targeting IκBζ through CDK4/6 inhibitors or modulating TME com-ponents can re-sensitize liver metastases to immunotherapy.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1292: Targeting convergent mechanisms of inefficient immunity in tumors and chronic infections
• Applicant Institution: Johannes Gutenberg-Universität Mainz
• Project Heads: Professor Dr. Carsten Deppermann; Professorin Dr. Daniela Kramer; Professor Dr. Detlef Schuppan, until 12/2025