A major discovery on melanoma immune evasion
An international team of researchers, including Coralie Capron, Professor Francesca Rapino, and Professor Pierre Close (all three FNRS researchers, members of the GIGA Institute), has published a major study in the journal Cell.
Led by Professor Carmit Levy (Tel Aviv University) and carried out in close collaboration with several international teams, including those from the GIGA Institute, this study sheds light on a previously unknown immune evasion mechanism used by melanoma cells, one of the most aggressive forms of skin cancer.
“This discovery reveals a previously unsuspected strategy by which melanoma cells directly hijack the T lymphocytes responsible for eliminating them,” explains Pierre Close.
Tumor vesicles that hijack the immune response
The researchers show that melanoma cells release large extracellular vesicles known as melanosomes, traditionally recognized for their role in melanin transport. Unexpectedly, these melanosomes display HLA molecules loaded with tumor antigens on their surface, enabling them to directly interact with CD8⁺ T-cell receptors.
These melanosomes therefore act as true immunological decoys:
- they capture cytotoxic T lymphocytes,
- induce incomplete T-cell activation,
- trigger mitochondrial dysfunction and, ultimately, apoptosis of T lymphocytes, thereby preventing an effective anti-tumor immune response.
A promising therapeutic target
The study also demonstrates that blocking melanosome secretion restores T-cell infiltration into tumors and limits tumor growth in preclinical models. These findings open new therapeutic avenues aimed at enhancing the efficacy of immunotherapies, particularly in patients who are resistant to immune checkpoint inhibitors.
“By targeting this immune evasion mechanism, it becomes possible to improve responses to existing immunotherapies and overcome certain forms of clinical resistance,” emphasizes Francesca Rapino.
A leading international collaboration
This work highlights the strength of the international collaborations developed by the GIGA Institute and the University of Liège, as well as the excellence of their teams in cancer biology and immuno-oncology, contributing to fundamental advances with the potential for major clinical impact.
Reference
Chemla et al.
HLA export by melanoma cells decoys cytotoxic T cells to promote immune evasion.
Cell, 2026.
Contacts pour le GIGA
FNRS Research Director, WELRI-WELBIO Investigator
FNRS Principal Investigator, WELRI-WELBIO Investigator
