On Wednesday 14 May 2025, the Luxembourg Institute of Health (LIH) announced that its scientists had helped decode how immune cells navigate the body, thus unlocking new potential for targeted therapies.
In a press release, LIH stated that researchers have discovered how chemokines and their receptors act like encrypted signals to guide immune cells through the body. Luxembourg scientists were closely involved with this discovery that has implications for cancer therapy, infection response and precision medicine.
LIH added that, in an international collaboration, published in Cell, scientists have revealed how cells interpret complex chemical "navigation signals" to move throughout the body - paving the way for designing smarter therapies that can guide immune cells to precise targets like tumours or infection sites. This study was led by researchers from St Jude Children’s Research Hospital and the Medical College of Wisconsin, with key contributions from the LIH.
LIH explained that at the heart of the discovery is the role of chemokines - small signalling proteins - and their receptors, known as GPCRs, which together direct how and where cells travel. While previous research struggled to explain how these molecules achieve such specificity given their structural similarities, the new study shows that the answer lies in tiny, disordered protein regions that function like digital encryption keys.
Scientists from LIH’s Immuno-Pharmacology and Interactomics group, under the direction of Dr Andy Chevigné and Dr Martyna Szpakowska, are reported to have played a central role in decoding this biological language. Their expertise, from the Department of Infection and Immunity and the advanced Interactomics and Biosensor platform (NanoLux), a high-resolution GPCR signalling tool developed in-house, was reported to be instrumental in experimentally validating how small changes to chemokines or receptors could reprogramme cellular behaviour.
Dr Andy Chevigné said: “It’s incredibly exciting to see how these short, unstructured protein segments - often overlooked - actually hold the key to highly selective cell communication. Our team used advanced technology platform to confirm that manipulating just a few amino acids can profoundly alter a chemokine’s function - this has enormous potential for immunotherapy and regenerative medicine.”
The findings are expected to have direct implications for developing engineered immune cells that better home in on tumours or therapeutic proteins that modulate the immune response with pinpoint accuracy. The researchers demonstrated they could alter a viral chemokine’s receptor preferences, proving the concept that selectivity in cell migration can be rationally designed.
Dr Martyna Szpakowska added that “this project showcases how data science, structural biology and cutting-edge pharmacology can come together to answer one of the most complex questions in immunology: how does a cell know where to go?”
The work was made possible through a collaboration with St Jude Children’s Research Hospital, where computational biologists built a data science framework to map chemokine-GPCR interactions like a codebook.
