New ways to separate graft-versus-host disease and graft-versus-tumour effects after allogeneic haematopoietic stem cell transplantation

Br J Haematol. 2013 Jan;160(2):133-45. doi: 10.1111/bjh.12115. Epub 2012 Nov 5.

Abstract

A major challenge to transplant immunologists and physicians remains the separation of harmful graft-versus-host disease (GvHD) and beneficial graft-versus-tumour (GvT) effects after allogeneic haematopoietic stem cell transplantation. Recent advances in our understanding of the allogeneic immune response provide potential new opportunities to achieve this goal. Three potential new approaches that capitalize on this new knowledge are considered in depth; the manipulation of organ-specific cytokines and other pro-inflammatory signals, the selective manipulation of donor effector T cell migration, and the development of cell-mediated immunosuppressive strategies using donor-derived regulatory T cells. These new approaches could provide strategies for local control of allogeneic immune responses, a new paradigm to separate GvHD and GvT effects. Although these strategies are currently in their infancy and have challenges to successful translation to clinical practice, all have exciting potential for the future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antigens, Neoplasm / administration & dosage
  • Cell Movement
  • Clinical Trials as Topic
  • Cytokines / metabolism
  • Graft Enhancement, Immunologic / methods*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Graft vs Tumor Effect* / drug effects
  • Graft vs Tumor Effect* / immunology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunity, Innate
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Lymphocyte Transfusion
  • Mice
  • Models, Immunological
  • Organ Specificity
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / transplantation
  • Translational Research, Biomedical / trends
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods
  • Transplantation, Homologous / immunology*
  • Vaccination

Substances

  • Antigens, Neoplasm
  • Cytokines
  • Immunosuppressive Agents