In a new study, researchers at the University Medical Centre Freiburg have shown that the immune architecture of liver cancer plays a decisive role in the success of immunotherapy. Using state-of-the-art methods, the researchers analysed the immune system at the cellular level and discovered three immune types in patients' tumours. The Freiburg doctors and scientists showed that these immune types directly influence how well patients respond to therapy with checkpoint inhibitors. The study was published on 30 September 2024 in the journal Gut.
"Our research shows that the spatial interaction of immune cells in tumour tissue significantly influences the success of immunotherapy," says the head of the study, Prof. Dr. Dr. Bertram Bengsch, Section Head at the Department of Internal Medicine II at the Freiburg University Medical Centre, member of the Cluster of Excellence CIBSS - Centre for Integrative Biological Signalling Studies and the German Consortium for Translational Cancer Research in Freiburg. "In the future, we could use this knowledge to identify patients for whom immunotherapy is particularly beneficial and should therefore be used early on, as well as those for whom additional therapies are useful."
Advances in immunotherapy for patients with liver cancer
Checkpoint inhibitors activate the immune system against liver cancer and are used in patients with advanced stages of the disease. However, some people respond better to the therapy than others. "Despite the great advances in treatment, there has been no way to assess the response of patients before starting therapy," emphasises Prof. Dr Robert Thimme, Medical Director of the Department of Internal Medicine II, who was involved in the study.
In order to understand whether the composition and organisation of the immune cells in the tumour are related to the response to checkpoint inhibitors, the researchers used imaging mass cytometry. "This allowed us to simultaneously and clearly identify the different cell types in the tissue," explains Henrike Salié, who carried out the investigations as part of her doctoral thesis. "Initially, I was surprised by the huge differences in the immune architecture between individual patients. The spatial distribution of the immune cells then allowed us to group the tumours in a meaningful way in immunological terms."
New ways to improve patient care
The researchers analysed samples from over 100 patients from international cohorts together with colleagues from Heidelberg and London. The team identified three main types of tumour tissue: immune-rich, compartmentalised and immune-poor. The current study shows that patients with immune-rich tumour tissue have the best chances of survival. A particularly high number of active immune cells were found here, including so-called CD8 T cells, which are considered crucial in the fight against tumour cells. Even in compartmentalised tumours, in which the immune cells were limited to connective tissue parts of the tumour, the checkpoint inhibitors showed an improved effect compared to patients with low immunity.
In the future, this classification could help to individually adapt the therapy as part of personalised medicine. "With this knowledge, we could use more customised therapies depending on the immune type and develop more targeted therapy options for patients with a less favourable prognosis," says Bengsch. Clinical trials can now build on the results to further investigate the efficiency of new combination treatments.
Original Publication
Henrike Salié, Lara Wischer, Antonio D’Alessio, Ira Godbole, Yuan Suo, Patricia Otto-Mora, Juergen Beck, Olaf Neumann, Albrecht Stenzinger, Peter Schirmacher, Claudia A M Fulgenzi, Andreas Blaumeiser, Melanie Boerries, Natascha Roehlen, Michael Schultheiß, Maike Hofmann, Robert Thimme, David J Pinato, Thomas Longerich, Bertram Bengsch (2024): Spatial single-cell profiling and neighbourhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma, In: Gut (30 September 2024). DOI: 10.1136/gutjnl-2024-332837