How are T lymphocytes’ fates sealed?
The ability to control T lymphocytes, which are key to the body’s immune response, opens up a whole range of therapeutic approaches, particularly for cancer. Immunologists and epigeneticists working together at Institut Curie have recently made another step forward in understanding these cells.
The immune system protects our body from both external attacks by bacteria and pathogens and internal attacks from cancer cells. When the system fails, our body is in danger. The fate of the T lymphocyte offers very significant opportunities for biological control of this process, an area of research that is being jointly investigated by the immunology team led by Sebastian Amigorena(1) and the epigenetics team led by Geneviève Almouzni(2). The T lymphocyte, or, more accurately, T lymphocytes, are today categorized into one of three major groups:
- “Naive”: T lymphocytes located in the lymph nodes, ready to respond to warnings issued by another immune system cell.
- “Effector”: T lymphocytes that are faced with a specific threat, such as an antigen, and are tasked with launching a targeted attack against it.
- “Memory”: T lymphocytes that have already faced a particular antigen and keep a record of this experience, meaning they can respond very quickly and effectively the next time the same enemy attacks.
They therefore provide life-long protection against attacks from pathogens and cancer cells. The fate of T lymphocytes is carefully controlled,
These Memory T lymphocytes have similar biological properties to stem cells and a long life-span. They can also produce Effector T lymphocytes, which then respond to attacks. “They therefore provide life-long protection against attacks from pathogens and cancer cells. The fate of T lymphocytes is carefully controlled,” explains Sebastian Amigorena. While a Naive T lymphocyte can become an Effector or Memory T lymphocyte, and a Memory T lymphocyte can become an Effector, once a lymphocyte becomes an Effector there is no going back. Luigia Pace, a postdoc at the Immunity and Cancer Unit (Inserm/Institut Curie), has made an important breakthrough in understanding how this locking mechanism works. Her work has been completed in close collaboration with Geneviève Almouzni and Jean-Pierre Quivy, CNRS Research Director in Nuclear Dynamics (CNRS/UPMC/Institut Curie), both of whom are passionate about the issue of cell fate.
Crossing disciplines to explore the immune system
The fate of T lymphocytes is determined by controlling the expression of key genes (activation, deactivation or repression). A major player in this control process, which comes via the field of epigenetics, is factor SUV39H1: a longstanding focus of Geneviève Almouzni’s team. SUV39H1 compacts or decompacts regions of the genome, influencing the expression of genes located in these regions. The same genome can therefore be used in different ways by the T lymphocyte. Once the appropriate gene panel has been activated and the fate of the Effector T lymphocyte is locked, the activation process for the gene program that would enable it to become a Memory cell is also locked – for good.
The two teams at Institut Curie are now aiming to understand how T lymphocytes acquire the ability to become Memory cells.
The researchers are excited about the potential applications of their discoveries.
The ability to manipulate epigenetic factors in order to control T lymphocytes means we can potentially program and reprogram at will. This represents a major opportunity to strengthen vaccine therapy and anti-PD-1 immunotherapy treatments. These new weapons in the fight against cancer are being actively explored at Institut Curie’s new immunotherapy center, which brings together researchers and physicians around a shared cause as part of the institute’s MC21 project.
(1) Sebastien Amigorena is a CNRS Research Director, Director of the Cancer Immunotherapy Center at Institut Curie and Director of the Immunity and Cancer Unit (Inserm/Institut Curie)
(2) Geneviève Almouzni is the CNRS Research Director at the Nuclear Dynamics Unit (CNRS/UPMC/Institut Curie) and Director of the Institut Curie Research Center.
