An early increase of CD56bright natural killer subset as dominant effect and predictor of response to extracorporeal photopheresis for graft-versus-host disease

BACKGROUND: CD56(bright) natural killer (NK) regulatory cells were recently shown to display a differential impact on the risk of developing extensive chronic graft-versus-host disease (GVHD). To date no study has definitively established which immune populations are most responsible for the immunomodulatory effects or response to extracorporeal photopheresis (ECP) for GVHD. STUDY DESIGN AND METHODS: To test the role of CD56(bright) NK cells in ECP, a prospective enhanced flow cytometry follow-up of immune subsets (CD19+, CD3+, CD3+/CD4+, CD3+/CD8+, CD3-/CD56+, CD3-/ CD56(bright), and CD3-/CD56thm) was performed in 32 patients with GVHD who underwent 552 procedures. RESULTS: An early increase of CD56(bright) NK cells was found as a hallmark effect to ECP, particularly during the first 3 months of treatment. This was also supported by the ability to predict for complete responses when this increase was expressed as a higher CD56(bright) versus CD56dIm NK cells ratio. Among the immune subsets tested, the only variable that had direct influence on response to ECP was a CD56(bright)/dim ratio more than 0.16 (hazard ratio [HR] 4.32, p = 0.014; HR 5.8, p = 0.007, at 2 and 3 months of ECP treatment, respectively). CONCLUSION: These findings argue for exploring strategies for priming a CD56(bright) NK cell expansion during ECP and providing additional and potentially relevant data for revisiting the underpinning cellular mechanisms of ECP that could generate that expansion.