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- Title
Lymph node-induced immune tolerance in chronic lymphocytic leukaemia: a role for caveolin-1.
- Authors
Gilling, Christine E.; Mittal, Amit K.; Chaturvedi, Nagendra K.; Iqbal, Javeed; Aoun, Patricia; Bierman, Philip J.; Bociek, Robert G.; Weisenburger, Dennis D.; Joshi, Shantaram S.
- Abstract
Emerging evidence indicates that the tumour microenvironment ( TME) regulates the behaviour of chronic lymphocytic leukaemia ( CLL). However, the precise mechanism and molecules involved in this process remain unknown. Gene expression profiles of CLL cells from lymph node ( LN), bone marrow ( BM) and peripheral blood ( PB) indicate overexpression of a tolerogenic signature in CLL cells in lymph nodes ( LN- CLL). Based on their role in B cell biology, the progression of CLL, or immune regulation, a few genes of this 83-gene signature were selected for further analyses. We observed a significant correlation between the clinical outcomes and the expression of CAV1 ( P = 0·041), FGFR1 isoform 8 ( P = 0·032), PTPN6 ( P = 0·031) and ZWINT ( P < 0·001). CAV1, a molecule involved in the regulation of tumour progression in other cancers, was seven-fold higher in LN- CLL cells compared to BM- and PB- CLL cells. Knockdown of CAV1 expression in CLL cells resulted in significantly decreased migration ( P = 0·016) and proliferation ( P = 0·04). When CAV1 was knocked down in B and T cell lines, we observed an inability to form immune synapses. Furthermore, CAV1 knockdown in CLL cells impaired their ability to form immune synapses with autologous T lymphocytes and allogeneic, healthy T cells. Subsequent analyses of microarray data showed differential expression of cytoskeletal genes, specifically those involved in actin polymerization. Therefore, we report a novel role for CAV1 in tumour-induced immunosuppression during the progression of CLL.
- Subjects
LYMPH nodes; IMMUNOLOGICAL tolerance; LYMPHOCYTIC leukemia; CAVEOLINS; GENE expression; STATISTICAL correlation; IMMUNOSUPPRESSION
- Publication
British Journal of Haematology, 2012, Vol 158, Issue 2, p216
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2012.09148.x