Extracorporeal photochemotherapy restores Th1/Th2 imbalance in patients with early stage cutaneous T‐cell lymphoma

Abstract

SUMMARYExtracorporeal photochemotherapy ( ECP) has been shown to be a potent activator of peripheral blood macrophages because it causes a marked release of macrophage-dependent proinflammatory cytokines, and it is therefore currently considered to be a safe and non-toxic immunomodulatory treatment. On this basis we studied the function of peripheral blood mononuclear cells (PBMC ) in eight patients with early stage (Ib) cutaneous T-cell lymphoma (CTCL), before and 1 year after ECP, together with their clinical and histological responses. In particular we evaluated in vitro phytohaemagglutinin (PHA)-stimulated proliferation and production of interleukin-4 (IL-4) and interferon-c (IFN-c) as well as lipopolysaccharide (LPS)-induced production of IL-12. Before treatment we observed that PBMC of patients produced significantly higher levels of IL-4 and lower levels of IFN-c and IL-12 than those of healthy control subjects. After 1 year of ECP, IL-4, IFN-c and IL-12 production no longer differed from that of control subjects. Moreover, we observed a good clinical result matched by histological response. Our data confirm that earlystage CTCL patients show a predominantly type-2 immune response that might be responsible for several immunological abnormalities found in this disease. We have demonstrated that ECP reverses the T-helper type 1/T-helper type 2 (Th1/Th2) imbalance and may therefore be considered an efficient biological response modifier.

Extracorporeal photopheresis (ECP) in the treatment of chronic graft-versus-host disease (GVHD)

“…26 ECP can also affect TH1/TH2 ratios. 27 However, our studies using a novel single cell cytokine assay showed no effect of ECP on TH1/TH2 ratios in patients with chronic cutaneous GVHD. 28,29 Our results indicate that ECP can benefit patients with cutaneous and mucosal chronic GVHD who have failed to improve on first-and second-line therapies.…”

Extracorporeal photopheresis in chronic graft-versus-host disease

“…In the context of CTCL, the restoration of Th1 cytokine secretion increases IL-12 production by monocytes, which might subsequently inhibit Th2 cytokine secreting cells that are believed to be responsible for the clinical manifestations of CTCL. 35 While monocytes appear to be resistant to the apoptotic effects of ECP, the induction of TNF-␣ secretion by photoactivated monocytes facilitates lymphocyte apoptosis. 36 Further, photoactivation of monocytes by ECP has also been shown to enhance their differentiation into CD83 + CD36 + dendritic cells capable of phagocytosing the apoptotic T cells.…”

Immunbiologische Effekte der extrakorporalen Photopherese

“…DiRenzo u. Mitarb. konnten zeigen, dass es bei Patienten mit kutanem T-Zell-Lymphom im Stadium Ib nach 1-jähriger ECP-Therapie nicht nur zur Erhöhung der CD36 + -Monozyten im peripheren Blut kommt, sondern auch zur Angleichung des Zytokin-Reaktionsprofils von peripheren Blutlymphozyten auf Stimulation mit Phytohämagglutinin in vitro im Vergleich zu gesunden Kontrollen [35]. Diese Effekte wurden dahingehend interpretiert, dass die Balance der pathologischen Th1/Th2-Immunantwort bei Patienten mit CTCL durch die ECP-Therapie wiederhergestellt wird.…”