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Title: Mechanisms of immune escape by B-cell lymphoma
Author: Lawrie, Alastair
ISNI:       0000 0004 6062 5037
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2016
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Many cancers, including lymphoma, are associated with increased numbers of T cells with suppressive properties, and it has been suggested that immune subversion is important in cancer pathogenesis. The ability of lymphoma cells to induce conventional CD25- T cells to adopt a regulatory phenotype was evaluated, with the aim of elucidating the factors and pathways governing this process and determining the clinical relevance. Regulatory T cell phenotype in both peripheral blood and nodal material from patients with lymphoma and healthy controls was also assessed. Preferential representation of Tregs in nodal tissue was noted with higher percentages seen than in peripheral blood. Contrary to previous studies, minimal evidence to suggest that lymphoma induces a regulatory phenotype from CD4+CD25- T cells was found. Furthermore, nodal Tregs displayed high expression of Helios and FOXP3, indicating a thymically-derived rather than induced origin. PD-1 expressing T cells were present in greater numbers in PBMCs from patients compared with healthy controls, suggesting an alternative reason for the immunosuppression that may be exhibited in these patients. These data support recruitment and amplification as the mechanism for the high proportion of Tregs seen in lymphoma. Hodgkin lymphoma is typified by a prominent reactive infiltrate and is the archetype of immune subversion in lymphoma. Inherited predisposition is demonstrated through familial and twin studies. Susceptibility loci have been identified in a number of genes that affect immune response, with the strongest association seen with the HLA region. 5 individuals with classical Hodgkin lymphoma from a family originating in North East Scotland were evaluated by linkage analysis and exome sequencing. Novel, shared variants predicted to disrupt protein function were identified in 2 genes on chromosome 3. Proximity to a previously described gene in familial Hodgkin lymphoma implicates this region as an important susceptibility locus.
Supervisor: Not available Sponsor: Friends of ANCHOR
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Lymphomas ; T cells ; Immunosuppression