Scientists from the Pasteur Institute and Inserm, based on a preclinical model, successfully stimulated an effective anti-tumor immune response by programming the death of malignant B cells. They demonstrated the efficacy of a triple therapy for treating forms of blood cancer, such as B-cell lymphomas and leukemias. This research was published in the journal Science Advances.
The goal of immunotherapy is to use a patient’s own immune system cells to destroy tumor cells. The new immunotherapy strategy utilizes necroptosis—a specific mechanism of cell death. This method artificially induces an explosive-like death of diseased (e.g., cancer) cells. During this so-called “explosion,” the contents of the cell are spilled out, sending an alarm signal to the immune system. This signal stimulates and trains immune cells so they can recognize and destroy harmful cells much more effectively.
This process releases what are called “alarm signals“—immune markers (known as DAMPs, or Damage-Associated Molecular Patterns). These markers signal the immune system that a threat exists.
Through the released markers, the immune system is trained: it learns how to more effectively recognize and destroy similar harmful cells in the future. In other words, necroptosis provides the immune system with “training material” so it can itself target and eliminate tumor cells.
The scientists investigated the effectiveness of necroptosis-based immunotherapy against hematological malignancies. Initially, they found that inducing necroptosis in malignant B cells was difficult due to the absence of the MLKL protein.
To overcome this obstacle, the researchers used a combination of three medications already existing in clinical practice. In the preclinical model, the induction of necroptosis was confirmed, and a potent immune response was observed, leading to the complete eradication of the leukemia.
Professor Philippe Bousso, the study’s lead researcher, explains: “The triple therapy we used forces tumor cells to die in a way that activates the immune system.”
Using innovative intravital imaging techniques, the scientists were able to monitor the interaction between immune and tumor cells in real-time. This approach suggests a potentially useful treatment method for B-cell lymphomas and leukemias.
