Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance.
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.
Kline
J
J
Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. jkline@medicine.bsd.uchicago.edu
Subbiah
S
S
Lazarus
H M
HM
van Besien
K
K
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000139:chemically induced; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006086:Graft vs Host Disease / Q000276:immunology*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D051379:Mice; D023421:Models, Animal; D017634:Self Tolerance / Q000187:drug effects; D014182:Transplantation, Autologous
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D016572:Cyclosporine