Molecular biologist Simon Haas is an expert on single-cell analyses. “We can produce extremely good snapshots,“ he says. “We can see which cells are present in a tissue, which cells are active at a given time, how they change, and which proteins they produce. That’s useful if you want to know how many active immune cells are meeting how many leukemia cells in the blood.”
But the scientists don’t yet have a good understanding of the interaction between the cells: “We know that the immune cells recognize the cancer cells and bind to them. What we don’t know, is which immune cells react with which cancer cells and what effect that has,” explains Haas. “Gaining that knowledge would show us why the immune system sometimes overcomes the leukemia cells and sometimes fails. And why immunotherapy is effective in some patients but not in others.”
Pairs instead of single cells
Haas is planning to adjust the method of single-cell analysis so that it can capture the interactions and communication between all immune cells and cancer cells. Haas and his team are located at the Berlin Institute for Molecular Systems Biology (BIMSB), which is part of the Max Delbrück Center and offers outstanding technical infrastructure for their work. “Instead of looking at individual cells, we’re aiming to investigate millions of cell pairs as they interact with each other. These doublets will tell us who is binding to whom, and what happens in the process.” Haas is interested in the signals that the cells exchange during their encounter, the stage of development they are currently in, and how the binding impacts the cells: Does it activate the immune cell? Does it kill the cancer cell?
The researchers working with Haas are starting by investigating mice that have leukemia. By looking at their blood, the team can see how the disease develops at different stages, how it advances, and how it can be stopped. Haas is also receiving support from his colleagues at Charité: The oncologists led by Professor Lars Bullinger, Director of the Department of Hematology, Oncology and Tumor Immunology on Campus Virchow-Klinikum, and Professor Ulrich Keller, Director of the Department of Hematology and Oncology on Campus Benjamin Franklin, are providing Haas with samples from leukemia patients. “Once we understand what disease stage the cells are in when they meet, and the developmental stage of the immune cells and the cancer cells, we’ll have a better understanding of how the immune response works and how the leukemia fights back,“ says Haas.
Why does immunotherapy fail?
Immunotherapies, which fight cancer using the body’s own immune system, are already being used successfully in the treatment of leukemia. But they only work in a fraction of the patients who receive them. “If we can take cell pairs from the blood of patients for whom the therapy worked and compare them with pairs from patients who weren’t so lucky, we’ll hopefully be able to identify which circumstances need to be present for the immune system to beat the leukemia.” The aim is to be able to predict which patients are likely to benefit from immunotherapy (which is a very complex and costly form of treatment), and how the therapy can be refined so that it works in more patients.
The ERC Starting Grant provides funding of roughly €1.5 million over five years. “But the global prestige of the award is almost more important than the money,” says Haas. The prize is considered a major seal of approval for junior researchers. It opens doors to other sources of funding and attracts high-quality applicants for doctoral and postdoc positions. This is good news for Haas, who now has the money to employ two doctoral students and one postdoc – which will help him fight leukemia more successfully than ever.