Tolerance and cancer: Mechanisms of tumor evasion and strategies for breaking tolerance

被引:235
作者
Mapara, MY
Sykes, M
机构
[1] Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA
[2] Humboldt Univ, Univ Med Ctr Charite, Dept Hematol & Oncol, Berlin, Germany
关键词
D O I
10.1200/JCO.2004.10.041
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1136 / 1151
页数:16
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