Cancer: a newly killed lymphocyte enters the ring

Treatment for invasive tumors is mainly based on CD8 T lymphocytes, which specifically detect and eliminate intracellular diseases and in the killing of cancer cells. But a large number of patients do not respond to these treatments. This led a research team from the Swiss Cancer Center Léman (SCCL, Switzerland) of the universities of Geneva (UNIGE) and Lausanne (UNIL), Ludwig Institute for Cancer Research (LICR), EPFL and CHUV to study CD4 T lymphocytes . . While these play a supportive role with CD8 T cells, the ability to directly detoxify tumor cells has been a matter of controversy. Using innovative nanoimaging technologies designed at the EPFL lab, the scientists found that when the CD4 T lymphocytes were placed in close contact with the cancer cells, up to a third of them could be killed. This find, article topic in Advances in science, important and broadening the therapeutic perspectives based on the administration of CD4 T lymphocytes to patients against conventional therapies.

When cancer cells expand in our bodies, our immune system kicks off. The first line of fighters capable of destroying tumor cells is CD8 T lymphocytes called cytotoxic T cells, supported by CD4 T lymphocytes. The last secret factors that help their predecessors are in many ways. “That’s why many cancer treatments are based on CD8 T lymphocytes,” begins Camilla Jandus, the study’s last author and professor in the Department of Pathology and Immunology in the UNIGE Faculty of Science and a consortium scientist at LICR. “Unfortunately, some patients do not respond to these treatments, so we have to find new ones.”

The SCCL team turned the focus to CD4 T lymphocytes, which offer valuable support to our immune system, as does Pedro Romero, a professor in the Department of Basic Oncology in the Faculty of Medicine and Biology of UNIL, who ‘explains: “These specialists have a much broader spectrum of action than CD8 T lymphocytes, and for a long time we did not know for sure whether they had the potential to differentiate into killing lymphocytes. “

To address this issue, the scientists studied CD4 T lymphocytes from approximately twenty patients with melanoma treated at CHUV. “While melanoma is not the most common skin cancer, it is the most lethal, and is particularly sensitive to immunotherapies,” Dr. Jandus confirms. The researchers removed the CD4 T lymphocytes from both blood and tumor fragments with the idea of ​​comparing them directly. Scattered tumor cells and CD4 T cells were synthesized to see their behavior separately. Observation devices were then required to bring a highly advanced solution down to the single cell stage. “We have created chunks of more than 20,000 microparticles of 65 picolitres (1 picolitre = 10-12 liters) that can accept CD4 T cells and tumor cells in each, and act as boxing rings,” said Hatice Altug, professor in the EPFL Bionanophotonic Systems laboratory. The researchers then plotted these thousands of wells simultaneously every five minutes for 24 hours to monitor the connections between the two cells from a large set of pairs. “We know it takes about two and a half hours for a CD8 to kill a tumor cell, so we decided to look at these boxing rings for 24 hours without knowing how, and if the CD4s would rework. , ”Continued Professor Altug.

To the great satisfaction of the scientists, high-throughput integration of dynamic imaging data showed that up to one-third of the CD4 T lymphocytes were successful in killing the closely related tumor cell within five hours. As Dr. Romero confirms: “These direct observations at the level of individual lymphocytes, first expressed at such a sensitive level, conclusively confirm the presence of CD4 T lymphocytes in is able to kill tumor cells. And this happens while the tumor is there. Cells are sometimes directed from their protective function to form a relationship with them. “

By analyzing the type of killing of CD4 T lymphocytes in detail, the scientists found that they produced SLAMF7 molecules, which stimulated their tumor-killing activity. “That is why we are now going to integrate and cultivate in vitro the best killing combination of CD4 T lymphocytes so that we can turn them into the true army of trillions of cells, which we can then be introduced into patients for whom CD8-based therapies do not work, “says Dr. Jandus. The human body naturally contains only a small number of CD4 T lymphocytes. guidance against tumors, and there is not enough to overcome them. ”The ability to see this close combat with our picowell chip paves the way for expanding the arsenal in the fight against cancer, which we now need to develop, “concluded Dr. Altug.

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