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Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration

Pasikowska, M., Walsby, Elisabeth Jane, Apollonio, B., Cuthill, K., Phillips, E., Coulter, E., Longhi, M. S., Ma, Y., Yallop, D., Barber, L. D., Patten, P., Fegan, C., Ramsay, A. G., Pepper, Christopher John, Devereux, S. and Buggins, A. G. S. 2016. Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration. Blood 128 (4) , pp. 563-573. 10.1182/blood-2016-01-683128

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Abstract

Several lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype and exhibit enhanced capacity for T-cell activation and superior immune synapse formation when compared to paired peripheral blood samples (PB). LN-derived CLL cells manifest a proliferative, CXCR4dimCD5bright, phenotype compared to those in the PB and higher expression of T-cell activation molecules including CD80, CD86 and HLA-DR. In addition, LN-CLL cells have higher expression of α4β1 (CD49d) which, as well as being a co-stimulatory molecule, is required for CLL cells to undergo transendothelial migration (TEM) and enter the proliferation centers of the LNs. Using an in-vitro system that models circulation and TEM, we showed that the small population of CLL cells that migrate are CXCR4dimCD5bright with higher CD49d, CD80, CD86 and HLA-DR compared to those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49dhi CLL cells showed enhanced capacity to activate T-cells compared to CD49dlo sub-populations from the same patient. Thus, although PB-CLL cells have reduced capacity to form immune synapses and activate CD4+ T-cells, this was not the case for LN-CLL cells or those with the propensity to undergo TEM. Taken together, our study suggests that CLL cell immunological function is not only modulated by microenvironmental interactions but is also a feature of a sub-population of PB-CLL cells that are primed for lymphoid tissue homing and interaction with T-cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: American Society of Hematology
ISSN: 0006-4971
Funders: Bloodwise
Date of First Compliant Deposit: 20 June 2016
Date of Acceptance: 27 May 2016
Last Modified: 11 Oct 2017 06:26
URI: http://orca.cf.ac.uk/id/eprint/92019

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