Extracorporeal Photopheresis: Tolerogenic or Immunogenic Cell Death? Beyond Current Dogma.

Abstract

Extracorporeal photopheresis (ECP) is an autologous cell therapy that is widely used for the treatment of T cell-mediated diseases. ECP has been FDA-approved for the treatment of cutaneous T cell lymphoma (CTCL) and has shown potent clinical benefits in various other (non-cancer) T cell-mediated diseases, such as graft versus host disease (GvHD), allograft rejection, as well as in autoimmune disorders, such as rheumatoid arthritis, psoriasis, systemic sclerosis, type 1 diabetes, and Crohn’s disease (1–3). The ECP treatment consists in the irradiation by UV-A in presence of a photosensitizer agent (8-methoxypsoralen) of PBMCs collected by apheresis (4). This will lead to an irreversible DNA crosslink by the psoralen, culminating by the apoptosis of virtually all the treated cells (5, 6). Then, the treated cells are re-infused to the patient. This repeated process leads to the improvement in patients’ clinical status, allowing the decrease or the disappearance of tumoral T cells in CTCL, or a decrease or a total disruption of immunosuppressive drugs, thus avoiding steroid-related side effects in GvHD (7). ECP has also shown benefits in cortico-refractory patients (8). Conversely to immunosuppressive treatments, ECP seems to selectively target allo- and auto-reactive T cells in GvHD and autoimmune diseases, respectively (called pathogenic T cells hereafter), without inducing systemic immunosuppression (9). Today, even if ECP has created real hopes for the treatment of these pathologies, its implementation is quite limited due to a relative empiric utilization due to the absence of prospective randomized clinical trials and a lack in the understanding of its mechanism of action (MoA).