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

journal contribution
posted on 2023-06-09, 09:29 authored by Marta Pasikowska, Elisabeth Walsby, Benedetta Apollonio, Kirsty Cuthill, Elizabeth Phillips, Eve Coulter, Maria Serena Longhi, Yun Ma, Deborah Yallop, Linda D Barber, Piers Patten, Chris Fegan, Alan G Ramsay, Christopher PepperChristopher Pepper, Stephen Devereux, Andrea PepperAndrea Pepper
everal 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 with paired peripheral blood (PB) samples. LN-derived CLL cells manifest a proliferative, CXCR4(dim)CD5(bright) phenotype compared with those in the PB and higher expression of T-cell activation molecules including CD80, CD86, and HLA-D-related (DR). In addition, LN-CLL cells have higher expression of a4ß1 (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 CXCR4(dim)CD5(bright) with higher CD49d, CD80, CD86, and HLA-DR compared with those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49d(hi) CLL cells showed an enhanced capacity to activate T cells compared with CD49d(lo) subpopulations from the same patient. Thus, although PB-CLL cells have a 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 immunologic function is not only modulated by microenvironmental interactions but is also a feature of a subpopulation of PB-CLL cells that are primed for lymphoid tissue homing and interaction with T cells.

Funding

In vitro modelling and therapeutic targeting of tumour cell migration in chronic lymphocytic leukaemia.; G2544; BLOODWISE; 18005

History

Publication status

  • Published

File Version

  • Published version

Journal

Blood

ISSN

1528-0020

Publisher

American Society of Hematology

Issue

4

Volume

128

Page range

563-573

Department affiliated with

  • Clinical and Experimental Medicine Publications

Research groups affiliated with

  • Haematology Research Group Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2017-12-20

First Open Access (FOA) Date

2017-12-20

First Compliant Deposit (FCD) Date

2017-12-20

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