Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V54
Höfundar / Authors: Teitur Sævarsson (1), Adrián López García de Lomana (2), Sólrún Melkorka Maggadóttir (3), Siggeir Fannar Brynjólfsson (3), Eiríkur Steingrímsson (2), Sebastien Wälchli (4), Else Marit Inderberg (4), Berglind Ósk Einarsdóttir (1)
Starfsvettvangur / Affiliations: 1 Department of Biomedical Science, Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 2 Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Reykjavík, Iceland 3 Department of Immunology, Landspítali, Reykjavík, Iceland. 4 Translational Research Unit, Department of Oncology, Oslo University Hospital, Norway
Kynnir / Presenter: Teitur Sævarsson
Melanoma cells frequently dedifferentiate in response to inflammation. This process entails a loss of melanocytic antigen expression, a gain in neural crest markers and occurs through downregulation of MITF, the master regulator of the melanocytic lineage. While antigen loss reduces immunogenicity, dedifferentiation may have broader immune related implications. We have recently described how dedifferentiating melanoma cells increase their expression of the immune checkpoint ligand PD-L1, multiple MHC complex genes and several immune modulating cytokines in response to IFN-γ, a clinically relevant inflammatory cytokine. Increased PD-L1 expression in dedifferentiated melanoma cells appears mediated through the JAKSTAT1-IRF1 axis, indicating enhanced canonical IFN-γ signaling following dedifferentiation. Preliminary data indicate that as expected, dedifferentiation impairs T cell recognition through loss of antigen. In addition, dedifferentiated melanoma cells may have impaired antigen-processing abilities. In conclusion, dedifferentiated melanoma cells develop a distinct immunological gene expression profile in addition to antigen loss. However, the functional relevance of this mechanism remains to be fully determined. In this talk, I will present these findings and describe a co-culture system we have established to explore how melanoma differentiation status affects interactions with cytotoxic T cells.