Mechanisms of Immune Tolerance in Leukemia and Lymphoma. Issue 7 (July 2017)

• Record Type: Journal Article
• Authors: Curran, Emily K.; Godfrey, James; Kline, Justin
• Is Part Of: Trends in immunology. Volume 38:Issue 7(2017)
• Page Start: 513
• Page End: 525
• Publication Date: 2017-07
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2017.04.004
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : The mechanisms through which immune responses are generated against solid cancers are well characterized and knowledge of the immune evasion pathways exploited by these malignancies has grown considerably. However, for hematological cancers, which develop and disseminate quite differently than solid tumors, the pathways that regulate immune activation or tolerance are less clear. Growing evidence suggests that, while numerous immune escape pathways are shared between hematological and solid malignancies, several unique pathways are exploited by leukemia and lymphoma. Below we discuss immune evasion mechanisms in leukemia and lymphoma, highlighting key differences from solid tumors. A more complete characterization of the mechanisms of immune tolerance in hematological malignancies is critical to inform the development of future immunotherapeutic approaches. Trends: Leukemia and lymphoma develop and progress in the same compartments in which immune responses are typically generated, suggesting that these diseases fail to trigger immune sensing mechanisms (immunological ignorance) or effectively impair antitumor immune responses when they do occur (immune evasion). Numerous immune evasion mechanisms are shared between solid and hematological cancers, but leukemia and lymphoma employ several 'exclusive' mechanisms of immune escape. Classical Hodgkin lymphoma is the prototypical example of an immunogenic hematological cancer that promotes immune evasion through a unique genetic mechanism of programmed death ligand 1 upregulation. T cell priming often occurs against solid cancer antigens but is followed by functional impairment in the tumor environment. Conversely, T cell tolerance in disseminated leukemia and lymphoma is regulated at the level of 'tolerogenic' antigen-presenting cells, leading to defective priming on initial antigen encounter.