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Checkpoint inhibitors only help a few patients with liver cancer / Study identifies immunological characteristics in tumor tissue that could predict treatment success / Potential for improving treatment

In a new study, researchers at the Medical Center - University of Freiburg show that the immune architecture of liver cancer plays a decisive role in the success of immunotherapy. Using state-of-the-art methods, the researchers analyzed the immune system at the cellular level and discovered three immune types in patients' tumors. The Freiburg physicians and scientists showed that these immune types directly influence how well patients respond to therapy with checkpoint inhibitors. The study was published on September 30, 2024 in the journal Gut.

"Our research shows that the spatial interaction of immune cells in tumor tissue significantly influences the success of immunotherapy," says Prof. Dr. Dr. Bertram Bengsch, head of the study and, as Heisenberg Professor, section head at the Department of Medicine II at the Medical Center - University of Freiburg. "In future, we could use this knowledge to identify patients for whom immunotherapy is particularly beneficial and should therefore be used at an early stage, 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 so far been no way to assess the response of patients before starting therapy," emphasizes Prof. Dr. Robert Thimme, Medical Director of the Department of Medicine II, who was involved in the study.

In order to understand whether the composition and organization of the immune cells in the tumor 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. "I was initially surprised by the huge differences in the immune architecture between the individual patients. The spatial distribution of the immune cells then allowed us to group the tumors in a meaningful way from an immunological perspective."

New ways to improve patient care

The researchers examined samples from over 100 patients from international cohorts together with colleagues from Heidelberg and London. The team identified three main types of tumor tissues: immune-rich, compartmentalized and immune-poor. The current study showed that patients with immune-rich tumor tissue have the best chances of survival. Here, a particularly high number of active immune cells were found, including so-called CD8 T cells, which are considered crucial in the fight against tumor cells. Even in compartmentalized 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 therapy in the context of personalized medicine. "With this knowledge, we could use more precisely tailored therapies depending on the immune type and develop more targeted therapy options for patients with a less good prognosis," says Bengsch, who is also a member of the Cluster of Excellence CIBSS - Centre for Integrative Biological Signalling Studies at the University of Freiburg and the German Consortium for Translational Cancer Research in Freiburg. Clinical studies can now build on the results to further investigate the efficiency of new combination treatments.

Original title of the study: Spatial single-cell profiling and neighborhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma
DOI: 10.1136/gutjnl-2024-332837
Link to the study:https://gut.bmj.com/content/early/2024/09/30/gutjnl-2024-332837