Regulation of the Immune Balance During Allogeneic Hematopoietic Stem Cell Transplantation by Vitamin D

One of the most promising therapeutic approaches for numerous hematological malignancies represents the allogeneic hematopoietic stem cell transplantation (allo-HSCT). One major complication is the development of the life-threatening graft-vs.-host disease (GvHD) which limits beneficial effects of graft-vs.-leukemia (GvL) responses during allo-HSCT. Strengthening GvL effects without induction of severe GvHD is essential to decrease the relapse rate after allo-HSCT. An interesting player in this context is vitamin D₃ since it has modulatory capacity in both preventing GvHD and boosting GvL responses. Current studies claim that vitamin D₃ induces an immunosuppressive environment by dendritic cell (DC)-dependent generation of regulatory T cells (Tregs). Since vitamin D₃ is known to support the antimicrobial defense by re-establishing the physical barrier as well as releasing defensins and antimicrobial peptides, it might also improve graft-vs.-infection (GvI) effects in patients. Beyond that, alloreactive T cells might be attenuated by vitamin D₃-mediated inhibition of proliferation and activation. Despite the inhibitory effects of vitamin D₃ on T cells, anti-tumor responses of GvL might be reinforced by vitamin D₃-triggered phagocytic activity and antibody-based immunotherapy. Therefore, vitamin D₃ treatment does not only lead to a shift from a pro-inflammatory toward a tolerogenic state but also promotes tumoricidal activity of immune cells. In this review we focus on vitamin D₃ and its immunomodulatory effects by enhancing anti-tumor activity while alleviating harmful allogeneic responses in order to restore the immune balance.