Extracorporeal Photopheresis Promotes IL-1β Production

Abstract

Extracorporeal photopheresis (ECP) is a widely used clinical cell-based therapy exhibiting efficacy in heterogenous immune-mediated diseases such as cutaneous T cell lymphoma, graft-versus-host disease, and organ allograft rejection. Despite its documented efficacy in cancer immunotherapy, little is known regarding the induction of immunostimulatory mediators by ECP. In this article, we show that ECP promotes marked release of the prototypic immunostimulatory cytokine IL-1β. ECP primes IL-1β production and activates IL-1β maturation and release in the context of caspase-1 activation in monocytes and myeloid dendritic cells. Of interest, IL-1β maturation by ECP was fully intact in murine cells deficient in caspase-1, suggesting the predominance of an inflammasome-independent pathway for ECP-dependent IL-1β maturation. Clinically, patient analysis revealed significantly increased IL-1β production in stimulated leukapheresis concentrates and peripheral blood samples after ECP. Collectively, these results provide evidence for promotion of IL-1β production by ECP and offer new insight into the immunostimulatory capacity of ECP.

Human Apoptotic Cells, Generated by Extracorporeal Photopheresis, Modulate Allogeneic Immune Response

“…Despite its therapeutic interest and wide-range coverage, the mechanisms of action of ECP are poorly known and sometimes contradictory. Surprisingly, it was reported that ECP promoted the release of prototypic immune-stimulatory cytokine IL-1β (8) and that the treated monocytes retained their ability to differentiate into fully functional dendritic cell (DC) that maturated and stimulated T cells as well as normal DC (9). On the other hand, a bunch of arguments, built on data collected mainly on rodents, strongly suggest that ECP-induced immunomodulation could be mediated largely by apoptosis resulting from exposure of mononuclear cells to UV-A or UV-B.…”

Extracorporeal Photopheresis: A Case of Immunotherapy Ahead of Its Time

“…A recent report with data from a mouse model and ECP-treated patients indicates that 8-MOP/UVA exposure has prominent immunostimulatory consequences closely associated with the release of IL-1β [64]. Monocytes and myeloid DC produced IL-1β after ECP in a mechanism predominantly independent of caspase-1 activation and in vitro culture of these cells showed a robust survival of professional APC for up to 7 days [64] (Fig. 2).…”

“…IL-1β is a potent inflammatory cytokine that synergizes with IL-2 to promote antitumoral cytotoxic activity in CD8+ T cells, inhibits the formation of Tregs, and plays a pathogenic role through the interactions of DC and T cells in inflammatory diseases such as rheumatoid arthritis [61-63]. A recent report with data from a mouse model and ECP-treated patients indicates that 8-MOP/UVA exposure has prominent immunostimulatory consequences closely associated with the release of IL-1β [64]. Monocytes and myeloid DC produced IL-1β after ECP in a mechanism predominantly independent of caspase-1 activation and in vitro culture of these cells showed a robust survival of professional APC for up to 7 days [64] (Fig.…”

Extracorporeal Photopheresis (ECP) and the Potential of Novel Biomarkers in Optimizing Management of Acute and Chronic Graft vs. Host Disease (GvHD)

“…The data for the effects of ECP on monocyte cell death are conflicting. While some groups report that monocytes are as susceptible to ECP-induced apoptosis as other PBMC (92)(93)(94), others show marked survival (95)(96)(97) or showed no greater levels of cell death than untreated controls (98,99). The reported preferential survival of monocytes may be facilitated by integrin-mediated survival signals generated through interaction of monocytes with plasma proteins bound to plastic surfaces in the ECP instrument, which subsequently directed differentiation into monocyte-derived dendritic cells (100).…”