MORPHEE : Mechanisms of Cell Death Induced by Extracorporeal Photochemotherapy

Extracorporeal photochemotherapy (ECP) is a cell therapy used for its immunomodulation and tolerance induction capabilities. Its main indications are the control of graft-versus-host (GVH) disease in hematopoietic cell allografts, treatment and control of rejection in solid organ transplantation and the treatment of cutaneous T-cell lymphoma. Data on the mechanisms of action of ECP remains very patchy. This lack of data limits the discussion on therapeutic regimens by disease.

ECP consists of repeated apheresis sessions to collect leukocytes from the patient. The cells are then photosensitized, irradiated with UVA and reinjected into the patient in a closed circuit. In the context of GVH, induced cell death would stimulate the expansion of regulatory cells (Treg), restore a Th1/Th2 balance and decrease Th17 polarization. The ECP also allows the expansion of Treg in solid organ transplantation. Conversely, ECP would restore or activate an antitumor immune response in cutaneous T lymphoma.

The type of cells collected and treated would play a major role in the effects obtained. However, these hypotheses must be consolidated, in particular by detailing the initial role of cell death. Several questions remain, on the chronology of cell death in the different treated subpopulations, on the uptake by phagocytes, but especially on the type of cell death induced according to the cell type (necroptosis, apoptosis, pyroptosis, autophagy). The data generated will allow for validation or detail of the mechanisms of resolution of the inflammation and/or the anti-tumour effect observed.