Biology of Graft-versus-Host Responses: Recent Insights

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many malignant and non-malignant hematological diseases. The curative effect of allo-HSCT results from both the chemotherapy and/or radiation in the conditioning regimen and the donor T mediated graft-versus-host (GVH) response against the malignancy known as a graft-versus-leukemia (GVL) effect. In most cases, the GVH response is not limited against the malignant cells, but also mediated against host epithelial cells causing graft-versus-host disease (GVHD). The safety and effectiveness of allogeneic transplants has increased substantially over the last several years. Despite the progress, GVHD and relapse remain the biggest hurdles for a more widespread and effective use of this potent therapy. Experimental data from recent years have provided deeper and better insights into the process of GVH responses. Emerging data have refined our understanding of the role of antigen presenting cells (APC) in GVHD. Novel molecular targets have been identified in donor T cell subsets and host non-hematopoietic cells that can potentially be exploited for mitigating GVHD and to better harness GVL. During recent years the role of various cytokines in GVHD continues to be explored. This work has led to improved understanding of potential causes for tissue specificity of GVHD. The role of host and donor microbiome in regulating GVH responses has been a subject of intense focus as well. Notable advances have been made in the defining various other aspects of GVH responses , but these go beyond the scope of this brief review. Herein we will focus on three specific aspects of GVH responses, namely 1) the evolving role of hematopoietic APCs as the regulators of GVHD, 2) novel strategies for enhancing GVL responses and 3) the recently identified molecular targets for mitigating GVH responses.