Frontiers in immunology · 2026
Interleukin-15 and innate effector cells as predictors of outcome in allogeneic hematopoietic cell transplantation.
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Warny Marie, Ostrowski Sisse Rye, Petersen Søren Lykke, Friis Lone Smidstrup, Kornblit Brian Thomas, Andersen Niels Smedegaard, Schjødt Ida, Larsen Margit Hørup, Møller Janne Amstrup, Haastrup Eva Kannik, Sengeløv Henrik, Minculescu Lia
Аннотация
INTRODUCTION: Immune reconstitution is a critical parameter in successful hematopoietic cell transplantation (HCT) and involves different cell types and a microenvironment including cytokines. Natural killer (NK) cells and γδ T cells are known to repopulate early after HCT and are proposed to have the intriguing capacity of mediating graft-versus-leukemia (GVL) effects without accompanying graft-versus-host-disease (GVHD). Interleukin-15 (IL-15) and interleukin-7 (IL-7) are key homeostatic cytokines, with effects on both T and NK cells, making these cytokines especially interesting in an HCT setting.
METHODS: In this prospective study, we investigated associations between IL-15 and IL-7, NK cells and γδ T cells, including activated subtypes, and clinical outcomes. We included 105 patients undergoing allogeneic HCT at a single-center institution. IL-15, IL-7, and extended T and NK cell phenotyping were measured longitudinally at fixed time points following HCT.
RESULTS: We found high IL-15 concentrations early post-transplant to be significantly associated with reduced overall survival, reduced relapse-free survival, and excess acute GVHD. Furthermore, IL-15 showed significant inverse correlations with NK cells and γδ T cells, including activated subtypes early after HCT, and with conventional T cells at later time points. IL-7 was significantly inversely correlated not only with conventional T cells but also with γδ T cells early after HCT.
DISCUSSION: These findings may suggest that early immune reconstitution of NK cells and γδ T cells is influenced by the bioavailability of IL-15 after HCT and that IL-15 could have a mechanistic effect in the activity of these innate effector cells. NK cells and γδ T cells are currently being investigated in several promising treatment settings, and IL-15 here may offer a potential benefit.
METHODS: In this prospective study, we investigated associations between IL-15 and IL-7, NK cells and γδ T cells, including activated subtypes, and clinical outcomes. We included 105 patients undergoing allogeneic HCT at a single-center institution. IL-15, IL-7, and extended T and NK cell phenotyping were measured longitudinally at fixed time points following HCT.
RESULTS: We found high IL-15 concentrations early post-transplant to be significantly associated with reduced overall survival, reduced relapse-free survival, and excess acute GVHD. Furthermore, IL-15 showed significant inverse correlations with NK cells and γδ T cells, including activated subtypes early after HCT, and with conventional T cells at later time points. IL-7 was significantly inversely correlated not only with conventional T cells but also with γδ T cells early after HCT.
DISCUSSION: These findings may suggest that early immune reconstitution of NK cells and γδ T cells is influenced by the bioavailability of IL-15 after HCT and that IL-15 could have a mechanistic effect in the activity of these innate effector cells. NK cells and γδ T cells are currently being investigated in several promising treatment settings, and IL-15 here may offer a potential benefit.