P05.01 Dynamic modulation of natural killer (NK) and cytokine induced killer (CIK) cells by extracorporeal photopheresis in chronic graft-versushost disease after hematopoetic stem cell transplantation

Background NK cells are central to immune reconstitution after allo-SCT and contribute to GVHD pathophysiology. Altered NK maturation and inhibitory phenotypes have been linked to persistent inflammation in cGVHD. ECP is widely used in steroid-refractory cGVHD, but its effects on NK-cell subset composition remain poorly defined.Aims To compare NK and checkpoint-expressing NK/CIK subsets between patients without GvHD (‘No-GvHD’, controls) and cGVHD patients receiving ECP at baseline and after 12 weeks.Methods ECP was administered using the THERAKOSTM CELLEXTM Photophoresis system. Peripheral Blood samples from cGVHD (n=14) and no-GVHD (n=14) allo-SCT recipients were analyzed at baseline and after 12-weeks follow-up. NK and CIK subsets were quantified by flow cytometry. Statistical analyses were performed.Results cGVHD displayed vs no-GvHD (baseline):↑ Cytokine-producing NK (CD56bri) cells↓TIGIT-expressing NK cells↓KLRG1-expressing and TIM3-expressing CIK cellsAfter 12 weeks from baseline, cGVHD patients displayed vs no-GvHD:↓Cytotoxic NK (CD56dimCD16+, CD56dimCD57+) cells↓TIGIT-expressing and KLRG1-expressing NK cells↓KLRG1-expressing CIK cellscGVHD patients displayed after 12 weeks ECP treatment:↓Cytokine-producing NK (CD56bri) cells↑TIGIT-expressing, KLRG1-expressing NK cells and 2B4+ expressing NK cells↓TIGIT -expressing and KLRG1-expressing CIK cellsConclusions cGVHD patients showed reduced cytotoxic NK signatures at follow-up compared with no-GVHD controls. During ECP, NK cells shifted toward increased inhibitory/stimulatory phenotypes and reduced cytokine-producing subsets, while CIK cells displayed an opposite trend. These data suggest differential NK/CIK remodeling as part of ECP’s immunomodulatory mechanism. Clinical correlations will be presented at the meeting.Funding This work was funded by an external collaborative research (ECR) grant provided by Therakos EMEA Limited