Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance

Bone Marrow Transplant. 2008 Mar;41(6):505-13. doi: 10.1038/sj.bmt.1705931. Epub 2007 Nov 19.


The absence of a graft-versus-malignancy (GVM) effect may be responsible for the higher relapse rate seen after autologous hematopoietic cell transplantation (auto-HCT) compared with allogeneic hematopoietic cell transplantation (allo-HCT). Acute GVHD developing after allo-HCT, however, is associated with significant morbidity and mortality. An autoimmune syndrome similar to acute GVHD has been reported to occur after auto-HCT and has been termed the 'auto-aggression' syndrome or autologous GVHD (auto-GVHD). Auto-GVHD tends to be milder than classical GVHD, most commonly involves the skin (rarely the gastrointestinal tract, liver or both) and often is self-limited. Auto-GVHD has been reported to occur both spontaneously and in subjects receiving post transplant immune modulation with CsA, IFN-gamma or the combination. The development of auto-GVHD depends upon the derangement of self tolerance either through administration of post transplant CsA, depletion of regulatory T cells following the preparative chemoradiotherapy or both. Self-reactive CD8(+) T cells paradoxically are able to recognize a self peptide antigen presented by MHC class II molecules and appear to mediate the syndrome. Many clinical trials have been performed using CsA with or without IFN-gamma in an attempt to induce auto-GVHD. While many patients do indeed develop the syndrome, any associated anti-tumor effect remains questionable to date. New strategies to exploit auto-GVHD and enhance a GVM effect such as through the depletion of regulatory T cells or through use of newer immunomodulatory agents may improve the efficacy of auto-HCT.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use
  • Autoimmune Diseases / chemically induced
  • Clinical Trials as Topic
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Graft vs Host Disease / immunology*
  • Graft vs Tumor Effect / immunology*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunity, Cellular / immunology
  • Immunosuppressive Agents / therapeutic use
  • Interferon-gamma / therapeutic use
  • Mice
  • Models, Animal
  • Self Tolerance / drug effects
  • Transplantation, Autologous


  • Antiviral Agents
  • Immunosuppressive Agents
  • Interferon-gamma
  • Cyclosporine