Li-Fraumeni syndrome: study provides new approaches for personalized care for those affected
The researchers from France and Germany (from left): Emilie Montellier of the Université Grenoble Alpes, MHH Professor Christian Kratz, Gaëlle Bougeard of the Université de Rouen Normandie and the late Professor Pierre Hainaut of the Université Grenoble Alpes. Copyrights (from left): Elotine Photo, Christian Wyrwa / wyrwa fotografie, Gaëlle Bougeard, Thomas Bianchin
Li-Fraumeni syndrome is a rare hereditary disease that significantly increases the risk of developing cancer. Almost all those affected are diagnosed with cancer at least once in their lives. A new study suggests that the immune system is partly responsible for why cancer occurs at very different ages and in different forms. This opens up new perspectives for personalized treatment approaches in the future. An international team published the results of the study in the journal Lancet.
Cross-national research can explain variable cancer risk
"Li-Fraumeni syndrome is caused by inherited changes in a gene called TP53, which normally helps to protect the body against cancer," explains Prof. Dr. Christian Kratz, Director of the Clinical Department of Paediatric Haematology and Oncology at Hannover Medical School (MHH) and co-initiator of the study. "Those affected have a high lifetime risk of developing cancer. In addition, the individual cancer risk can vary significantly even within the same family." In the transnational study, in which leading representatives from the Université Grenoble Alpes, the Université de Rouen Normandie from France and the MHH were involved, the researchers wanted to understand the causes of this variability in more detail.
Immune cells can recognize gene changes recognize
The researchers investigated whether the body's own immune system could play a role in the development of cancer.
"We focused on how various changes in the TP53 gene are recognized by immune cells," explains Emilie Montellier from the Université Grenoble Alpes. "Some altered forms of the TP53 protein can produce small fragments that the immune system recognizes as abnormal, which is associated with a reduced risk of cancer."
By analyzing genetic and clinical data from thousands of people with Li-Fraumeni syndrome, the researchers identified a clear pattern: affected individuals who carried variants in the TP53 gene that were more likely to be recognized by the immune system tended to develop cancer later in life. They were also less likely to develop some of the cancers most commonly associated with Li-Fraumeni syndrome, such as bone and soft tissue sarcomas.
Reduced overall risk of cancer
The findings suggest that the immune system influences how a person's inherited cancer risk develops over the course of their lifetime. While immune recognition does not prevent the development of cancer in people with Li-Fraumeni syndrome, it may help to lower the overall risk by delaying the onset of cancer or changing the type of cancers that occur.
"Our work has no immediate impact on medical care, but opens up new possibilities for personalized approaches in the future," explains Gaëlle Bougeard of the Université de Rouen Normandie. "Information about the specific TP53 variant and the background of a person's immune system can help physicians to better adapt cancer monitoring and prevention strategies in the future."
"More generally, these results show how interactions between genetic variations and the immune system can influence cancer risk - not only in Li-Fraumeni syndrome, but possibly also in other hereditary cancers," adds Professor Kratz, whose research is supported by the German Childhood Cancer Foundation.
An obituary for Prof. Dr. Pierre Hainaut, who was instrumental in advancing the study and tragically passed away after submitting the manuscript, can be found here.
Text: Jana Illmer
You can findthe original publication here.