Prof. Clemens Schmitt, chair of Hematology and Internal Oncology at the JKU’s Faculty of Medicine remarked, “In the field of oncology, predicting whether or not patients respond to drugs such as immunochemotherapy is crucially important in order to improve treatment and figure out the reasons why previous treatment failed." An article by Prof. Schmitt and his team in the scientific publication "Nature Communications" focuses on just how physicians can better assess a patient’s chances to be cured of lymph gland cancer, specifically in "diffuse large cell B-cell lymphoma (DLBCL)" - even before therapy begins.

DLBCL is a malignant lymphatic system disease that affects the lymphocytes, to be precise. They are a special subgroup of white blood cells responsible for defending against pathogens. The majority of patients diagnosed with aggressive lymphoma can be treated effectively with modern immunochemotherapy. However, approximately one-third of these patients do not respond to this particular treatment. The head of the Department of Hematology and Internal Oncology added, “We are urgently looking for new approaches for these patients. We are focusing particularly on the biological changes in the tumor cells under treatment, especially the so-called 'cellular senescence."

Stopping Cell Division

All clinical cancer treatments aim to destroy as many tumor cells as possible while preventing additional cells from spreading in the body. Cellular senescence plays an important role here as an alternative to killing cells by halting cell division instead. Using a lymphoma-infected mouse model, researchers have explored just how important the senescence program is under conditions similar to clinical practice. The findings on the molecular control and clinical significance of cellular senescence (only possible in genetically manipulated immunocompetent mice) were then reflected back to the patient's DLBCL situation and tested for validity.

In particular, researchers succeeded in deriving a gene signature called "SUVARness" in an animal model. When translated into a corresponding human signature, this could serve as a biomarker and could reliably predict the success rate for senescence-dependent treatment in DLBCL patients.

Findings on senescence ability from mouse model-based research can indeed be transferred to humans. The studies performed on the mouse model are very similar to a clinical study in humans. The gene signature derived from the mouse was successfully applied in several large, independent study populations that included several hundred patients. Prof. Schmitt remarked: "At the clinic, we are trying to transfer mouse findings directly and make them available to patients. It would be technically unethical and practically impossible to conduct this kind of research on cancer patients."

These findings could better assess the prognosis for newly diagnosed DLBCL patients. Prof. Schmitt is looking toward the future and added: "The next step will be to be able to use this new information as part of the treatment."

The article “H3K9me3-Mediated Epigenetic Regulation of Senescence in Mice Predicts Outcome of Lymphoma Patients” has been published in the renowned scientific journal “Nature Communications”.