Laura Mondragon Martinez, PhD

Angioimmunoblastic T-cell lymphoma (AITL) is a type of blood cancer affecting mature individuals. It does not present symptoms until the late stages of the disease, when it is usually diagnosed. As a consequence, patient survival does not exceed 32% after 5 years. Its origin lies in a type of T-cell called T follicular helper (Tfh). Tfh activate B cells to initiate the immune response when they detect the presence of infectious agents. Their function ends once this threat has been neutralised, at which point they stop stimulating B cells. However, for unknown reasons, in AITL, Tfh do not stop activating B cells even when the external threat has been neutralised. As a consequence, there is an increase in the number of T and B cells leading to the onset of the disease. To date, there is no specific therapy for its treatment, which greatly reduces the patient's chances of survival. In this project, we propose a new specific therapy from the study of the Apaf-1 heterozygous KO mouse model which mimicks AITL disease as we have observed the presence of a new type of follicular helper T cells that we believe are the true origin of the disease. Thus, we propose in this project to test a new therapy based on the use of antibodies that neutralise and destroy these defective T cells in order to stop this massive division of T and B cells and cure the patient. This therapy will be tested both in animals and in samples from AITL patients.