Extracorporeal Photopheresis: From Animal Models to Clinical Practice

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy characterized by the exposure of leukocytes to 8-methoxypsoralen and UV light irradiation, followed by reinfusion of the treated cells into the patient. ECP is considered a safe and well-tolerated procedure that preserves the beneficial aspects of immunity, such as antitumor and antiviral activities, with a low rate of side effects. Currently, ECP is used for the treatment of immune-mediated conditions, such as cutaneous T-cell lymphoma, graft-versus-host disease, solid organ transplant rejection, and autoimmune disorders. ECP is an immunomodulatory therapy characterized by multiple complex events that lead to the modulation of the immune response. Modifying the activity of myeloid antigen-presenting cells with apoptotic cell remnants is key to the therapeutic action of ECP; however, because the pathological roles of macrophages and dendritic cells are context specific, the precise effects of ECP vary between different diseases. Consequently, we need a much better understanding of the immunology and pharmacology of ECP to extend its use in solid organ transplantation and beyond. During the past decades, important advances were made using animal models of ECP, leading to a better mechanistic understanding and its more rational use in many T cell-mediated conditions. This review summarizes the available information on animal models of ECP, providing insights into the mechanisms of action, therapeutic applications, limitations, and translational potential from preclinical animal models to human clinical practice.