Advances in the understanding of acute graft-versus-host disease

Allogeneic stem cell transplantation (SCT) remains the definitive immunotherapy for malignancy. However, morbidity and mortality due to graft-vs.-host disease (GVHD) remains the major barrier to its advancement. Emerging experimental data highlights the immuno-modulatory roles of diverse cell populations in GVHD, including regulatory T cells, natural killer (NK) cells, NK T cells, γδ T cells, and antigen presenting cells (APC). Knowledge of the pathophysiology of GVHD has driven the investigation of new rational strategies to both prevent severe GVHD and treat steroid-refractory GVHD. Novel cytokine inhibitors, immune-suppressant agents known to preserve or even promote regulatory T-cell function and the depletion of specific alloreactive T-cell sub-populations all promise significant advances in the near future. As our knowledge and therapeutic options expand, the ability to limit GVHD whilst preserving anti-microbial and tumour responses becomes a realistic prospect.