title: Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance.
abstract: The development of malignant disease might be seen as a failure of immune surveillance. However, not all tumors are naturally immunogenic, and even among those that are immunogenic, the uncontrolled rapid growth of a tumor may sometimes out-run a robust immune response. Nevertheless, recent evidence suggests that mechanisms of tolerance that normally exist to prevent autoimmune disease may also preclude the development of an adequate antitumor response and that tumors themselves have the ability to thwart the development of effective immune responses against their antigens. A major challenge has been to develop approaches to breaking this tolerance in tumor-bearing hosts, and recent advances in our understanding of antigen presentation and tolerance have led to some promising strategies. An alternative approach is to use T cells from nontumor-bearing, allogeneic hosts in the form of lymphocyte infusions, with or without hematopoietic cell transplantation. Immunotherapy may occur in this setting via the response of nontolerant, tumor antigen-specific T cells from nontumor-bearing hosts or via the powerful destructive effect of an alloresponse directed against antigens shared by malignant cells in the recipient. Approaches to exploiting this beneficial effect without the deleterious consequence of graft-versus-host disease in allogeneic hematopoietic cell recipients are discussed.
authors.affiliation: Department of Hematology and Oncology, University Medical Center Charité, Campus Virchow Klinikum, Humboldt University Berlin, Germany.
authors.forename: Markus Y
authors.initials: MY
authors.lastname: Mapara
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D033581:Stem Cell Transplantation; D014181:Transplantation Immunology; D019139:Tumor Escape
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines