The role of immunoediting in lymphomas of immune-privileged sites

Marije Booman

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Diffuse large B cell lymphomas (DLBCL) can be found at several different locations. DLBCL in the central nervous system or the testis are 'Immune-privileged site-associated' diffuse large B-cell lymphomas (IP-DLBCL). They differ from other DLBCL in several clinical and molecular aspects. The most striking characteristic of IP-DLBCL is the loss of expression of human leukocyte antigen (HLA), often associated with deletions of the HLA region on chromosome 6p21.3. The research in this thesis aims to gain more insight into the molecular background of the biological behavior of IP-DLBCL. Loss of HLA expression in IP-DLBCL was associated with loss of expression of numerous genes involved in the immune response and with a lower number of immune cells. The common chromosomal aberrations also deregulated genes that are involved in the immune response or cell death. These results indicate the importance of the regulation of the anti-tumor immune response in IP-DLBCL, loss of HLA expression probably being an immune escape mechanism. Apart from the loss of HLA expression, additional characteristics of IP-DLBCL that separate them from other DLBCL were investigated. IP-DLBCL have an 'activated B cell-like' expression profile. IP-DLBCL also share some characteristic genomic aberrations. These findings support the classification of IP-DLBCL as a separate subgroup within DLBCL in general. To complete the thesis a model is proposed for IP-DLBCL lymphomagenesis based on the principle of immunoediting, in which the interaction between the lymphoma and its environment shapes the final characteristics of the IP-DLBCL.
Originele taal-2English
KwalificatieDoctor of Philosophy
Begeleider(s)/adviseur
  • Kluin, Philip, Supervisor
Uitgever
Gedrukte ISBN's9789036734127
StatusPublished - 2008

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