Press Release
Luxembourg Scientists Help Crack the Code of Cellular GPS
LIH scientists help decode how immune cells navigate the body, unlocking new potential for targeted therapies
Researchers have discovered how chemokines and their receptors act like encrypted signals to guide immune cells through the body. A major contribution from Luxembourg scientists enabled this discovery, with implications for cancer therapy, infection response, and precision medicine.
In a major 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 landmark study was led by researchers from St. Jude Children’s Research Hospital and the Medical College of Wisconsin, with key contributions from the Luxembourg Institute of Health (LIH).
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, 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, were instrumental in experimentally validating how small changes to chemokines or receptors could reprogram cellular behaviour.
It’s incredibly exciting to see how these short, unstructured protein segments—often overlooked—actually hold the key to highly selective cell communication,
said Dr Andy Chevigné, co leader of the Immuno-Pharmacology and Interactomics group at LIH.
“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 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.
“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?” Added Dr Martyna Szpakowska, co leader of the Immuno-Pharmacology and Interactomics group at LIH and second author of the manuscript.
The work was made possible through a fruitful collaboration with St. Jude Children’s Research Hospital, where computational biologists built a data science framework to map chemokine-GPCR interactions like a codebook. The resulting online resource is freely available to the scientific community and could serve as a blueprint for designing next-generation therapeutics.
The article was published in Cell under the full title: “Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network.”
Funding and collaborations
The study was supported by grants from the Medical Research Council, the National Institutes of Health, the Luxembourg Institute of Health NanoLux Platform, the Luxembourg National Research Fund, Cancer Foundation Luxembourg, F.R.S.-FNRS-Télévie, the St. Jude GPCR Research Collaborative, AstraZeneca Blue Sky Fund, the Swiss National Science Foundation, the Cancer Prevention and Research Institute of Texas, the Alfred P. Sloan Scholar Research Fellowship, the Andrew Sabin Family Foundation Fellowship, the Ovarian Cancer Research Alliance and ALSAC, the fundraising and awareness organization of St. Jude.
About the Luxembourg Institute of Health (LIH)
The Luxembourg Institute of Health (LIH) is a public biomedical research organisation focused on precision health and invested in becoming a leading reference in Europe for the translation of scientific excellence into meaningful benefits for patients.
The LIH places the patient at the heart of all its activities, driven by a collective obligation towards society to use knowledge and technology arising from research on patient derived data to have a direct impact on people’s health. Its dedicated teams of multidisciplinary researchers strive for excellence, generating relevant knowledge linked to immune related diseases and cancer.
The institute embraces collaborations, disruptive technology and process innovation as unique opportunities to improve the application of diagnostics and therapeutics with the long-term goal of preventing disease.
About St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is leading the way the world understands, treats and cures childhood cancer, sickle cell disease, and other life-threatening disorders. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude shares the breakthroughs it makes to help doctors and researchers at local hospitals and cancer centers around the world improve the quality of treatment and care for even more children. To learn more, visit stjude.org, read St. Jude Progress, a digital magazine, and follow St. Jude on social media at @stjuderesearch.