Lymph node-induced immune tolerance in chronic lymphocytic leukaemia: a role for caveolin-1

British Journal of Haematology
Christine E GillingShantaram S Joshi

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 lymphocyt...Continue Reading

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Citations

Aug 13, 2013·PloS One·Amit K MittalShantaram S Joshi
Oct 10, 2012·American Journal of Hematology·Sonia FabrisAntonino Neri
Sep 9, 2017·Leukemia & Lymphoma·Ashima ShuklaShantaram S Joshi
Jul 26, 2018·Oncotarget·Jacob E Robinson, Christine E Cutucache
Dec 27, 2016·Frontiers in Oncology·Chelsey L Patten, Christine E Cutucache
Nov 27, 2020·Biochemical Society Transactions·Anna-Maria Schaffer, Susana Minguet
Apr 2, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fabiola Cervantes-GomezVarsha Gandhi

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