Unravelling the role of the microenvironment in chronic lymphocytic leukaemia: T helper cell support of cancer cells
Appears in the following Collection
AbstractAs part of the adaptive immune response, B cells are central to our defence against an unlimited type of pathogens. However, B cells and antibodies can be harmful in allergic or in autoimmune responses. Inherited or acquired problems in B cell development or function can lead to immunodeficiency. And last but not least, B cells may also become malignant B cells Chronic lymphocytic leukemia (CLL) is a disease of clonal malignant B-cells that proliferate in bone marrow and lymph nodes. The microenvironment supports malignant B cells by providing anti-apoptotic signals and signals that help the B cells grow. Macrophages, dendritic cells, stromal cells, mesenchymal cells, follicular dendritic cells and T cells are part of this microenvironment. In this thesis we try to unravel the role of Th cells as part of this microenvironment in CLL. Here we show that a subset of Th cells support CLL cell growth in vitro and in vivo in a mouse model. Targeting treatments not only against the cancerous cell but also to its microenvironment may help patient survival.
List of papers
|Paper I: Chronic lymphocytic leukaemia cells are activated and proliferate in response to specific T helper cells. Os A, Bürgler S, Ribes AP, Funderud A, Wang D, Thompson KM, Tjønnfjord GE, Bogen B, Munthe LA. Cell Rep. 2013 Aug 15;4(3):566-77. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.celrep.2013.07.011|
|Paper II: Chronic lymphocytic leukaemia cells express CD38 in response to Th1 cell-derived IFN-γ by a T-bet-dependent mechanism. Bürgler S, Gimeno A, Parente-Ribes A, Wang D, Os A, Devereux S, Jebsen P, Bogen B, Tjønnfjord GE, Munthe LA. J Immunol. 2015 Jan 15;194(2):827-35. The paper is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.4049/jimmunol.1401350|
|Paper III: Spleen tyrosine kinase inhibitors reduce CD40L-induced proliferation of chronic lymphocytic leukaemia cells but not normal B cells. Parente-Ribes A, Skånland SS, Bürgler S, Os A, Wang D, Bogen B, Tjønnfjord GE, Taskén K, Munthe LA. Haematologica. 2016 Feb;101(2):e59-62. The article is included in the thesis. Also available at: https://doi.org/10.3324/haematol.2015.135590|
|Paper IV: Epstein-Barr virus specific Th cells promote EBV-infection and proliferation of CLL cells. Parente-Ribes A, Bürgler S, Os A, Wang D, Delabie J, Tjønnfjord GE, Munthe LA. Manuscript. To be published. The paper is not available in DUO awaiting publishing.|