The role of CD56bright natural killer cells in extracorporeal photopheresis

Extracorporeal photopheresis (ECP) is an immunomodulatory therapeutic procedure which includes leukapheresis of peripheral blood, then separation of the buffy coat, and finally the irradiation of cells before re-infusion. ECP is commonly used either in combination with infliximab or monotherapy as a second-line therapy for patients with graft-versus-host disease (GvHD) who are dependent or refractory to steroids.

Pastora Iniesta from the Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain, and colleagues assumed that CD56^bright NK cells may increase in patients with GvHD who respond to ECP therapy and may correlate with response rates. The researchers prospectively studied blood subsets during ECP treatment.

Patients and methods:

• Enhanced flow cytometry was used to study the following molecules: CD19+, CD3+, CD3+/CD4+, CD3+/CD8+, CD3-/CD56+, CD3-/ CD56^bright, and CD3-/CD56^dim
• N = 32 patients were enrolled and received ECP
  • aGvHD: n = 11; median age = 46 years (range, 41–62)
  • cGvHD: n = 21; median age = 49 years (range, 42–57)

Key findings:

• There was a significant increase in the level of CD56 NK cells during ECP: χ2 = 33.680, P ≤ 0.001
• Higher level of CD19 cells was found: χ2 = 9.878, P = 0.043
• There was a significant difference in the level of CD56^bright NK following ECP: χ2 = 35.358, P ≤ 0.001
• CD56^dim NK cells significantly increased in the course of ECP: χ2 = 23.960, P ≤ 0.001
• Complete response (CR) rates: 7/11 aGvHD patients (64%) and 8/21 cGvHD cases (39%)

In conclusion, this study showed elevated levels of CD56^bright NK cells after ECP therapy. The authors stated that “an early increase of CD56^bright NK cells may be involved in the complex interplay of immunologic cells in exerting tolerance induced by ECP, both in aGvHD and cGvHD. This is also supported by the ability of the CD56^bright to CD56^dim NK cells ratio to predict for CR to the phototherapy.” These findings require independent validation including further exploring approaches for priming CD56^bright NK cell expansion during ECP and revisiting the underpinning cellular mechanisms of ECP that could induce cell expansion.